Skip to main content
SpringerLink
Log in

Tumor-Infiltrating Dendritic Cells: The Pathologist’s Perspective

  • Chapter
  • First Online:
Dendritic Cells in Cancer

Abstract

In order to perform immunosurveillance and initiate antitumor immune response, dendritic cells must be physically present in malignant tissues. This chapter summarizes data on the density and functional status of tumor-infiltrating dendritic cells in different types of human malignant neoplasms, generated by immunohistochemistry methods. The results show that density and maturation of tumor-associated dendritic cells vary in specific types of tumors and correlate with histologic grade and clinical stage of the disease. In majority of cases there is positive correlation between intratumoral dendritic cell density and favorable disease prognosis; however, certain exceptions are present. Possible mechanisms of tumor-related alterations of dendritic cell homing, survival, and maturation at the tumor site are discussed.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 169.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Aalamian, M., Tourkova, I. L., Chatta, G. S., Lilja, H., Huland, E., Huland, H., Shurin, G. V. and Shurin, M. R. 2003. Inhibition of dendropoiesis by tumor derived and purified prostate specific antigen. J Urol 170:2026–2030.

    PubMed  CAS  Google Scholar 

  • Adema, G. J., de Vries, I. J., Punt, C. J. and Figdor, C. G. 2005. Migration of dendritic cell based cancer vaccines: in vivo veritas? Curr Opin Immunol 17:170–174.

    PubMed  CAS  Google Scholar 

  • Ambe, K., Mori, M. and Enjoji, M. 1989. S-100 protein-positive dendritic cells in colorectal adenocarcinomas. Distribution and relation to the clinical prognosis. Cancer 63:496–503.

    PubMed  CAS  Google Scholar 

  • Aso, T., Ogawa, Y., Naoe, M., Fukagai, T., Yoshida, H. and Kushima, M. 2004. [Immunohistochemical analysis of CD83, CD8 and CD4 positive cells in renal cell carcinoma]. Nippon Hinyokika Gakkai Zasshi 95:645–650.

    PubMed  Google Scholar 

  • Baleeiro, R. B., Anselmo, L. B., Soares, F. A., Pinto, C. A., Ramos, O., Gross, J. L., Haddad, F., Younes, R. N., Tomiyoshi, M. Y., Bergami-Santos, P. C. and Barbuto, J. A. 2008. High frequency of immature dendritic cells and altered in situ production of interleukin-4 and tumor necrosis factor-alpha in lung cancer. Cancer Immunol Immunother 57(9):1335–1345.

    Google Scholar 

  • Balkir, L., Tourkova, I. L., Makarenkova, V. P., Shurin, G. V., Robbins, P. D., Yin, X. M., Chatta, G. and Shurin, M. R. 2004. Comparative analysis of dendritic cells transduced with different anti-apoptotic molecules: sensitivity to tumor-induced apoptosis. J Gene Med 6:537–544.

    PubMed  CAS  Google Scholar 

  • Bell, D., Chomarat, P., Broyles, D., Netto, G., Harb, G. M., Lebecque, S., Valladeau, J., Davoust, J., Palucka, K. A. and Banchereau, J. 1999. In breast carcinoma tissue, immature dendritic cells reside within the tumor, whereas mature dendritic cells are located in peritumoral areas. J Exp Med 190:1417–1426.

    PubMed  CAS  Google Scholar 

  • Bergeron, A., El-Hage, F., Kambouchner, M., Lecossier, D. and Tazi, A. 2006. Characterisation of dendritic cell subsets in lung cancer micro-environments. Eur Respir J 28:1170–1177.

    PubMed  CAS  Google Scholar 

  • Bigotti, G., Coli, A. and Castagnola, D. 1991. Distribution of Langerhans cells and HLA class II molecules in prostatic carcinomas of different histopathological grade. Prostate 19:73–87.

    PubMed  CAS  Google Scholar 

  • Bontkes, H. J., Ruizendaal, J. J., Kramer, D., Meijer, C. J. and Hooijberg, E. 2005. Plasmacytoid dendritic cells are present in cervical carcinoma and become activated by human papillomavirus type 16 virus-like particles. Gynecol Oncol 96:897–901.

    PubMed  Google Scholar 

  • Brustmann, H. 2006. Galectin-3 and CD1a-positive dendritic cells are involved in the development of an invasive phenotype in vulvar squamous lesions. Int J Gynecol Pathol 25:30–37.

    PubMed  Google Scholar 

  • Buckanovich, R. J., Sasaroli, D., O'Brien-Jenkins, A., Botbyl, J., Conejo-Garcia, J. R., Benencia, F., Liotta, L. A., Gimotty, P. A. and Coukos, G. 2006. Use of immuno-LCM to identify the in situ expression profile of cellular constituents of the tumor microenvironment. Cancer Biol Ther 5:635–642.

    PubMed  CAS  Google Scholar 

  • Cai, X. Y., Gao, Q., Qiu, S. J., Ye, S. L., Wu, Z. Q., Fan, J. and Tang, Z. Y. 2006. Dendritic cell infiltration and prognosis of human hepatocellular carcinoma. J Cancer Res Clin Oncol 132:293–301.

    PubMed  Google Scholar 

  • Cao, F. M., Zhang, X. H., Yan, X., Wang, J. L., Wang, X. L., Zhang, Z. G., Shen, H. T. and Wang, F. R. 2005. [Prognostic significances of natural killer cells and dendritic cells infiltrations in esophageal squamous cell carcinoma]. Ai Zheng 24:232–236.

    PubMed  CAS  Google Scholar 

  • Caux, C., Ait-Yahia, S., Chemin, K., de Bouteiller, O., Dieu-Nosjean, M. C., Homey, B., Massacrier, C., Vanbervliet, B., Zlotnik, A. and Vicari, A. 2000. Dendritic cell biology and regulation of dendritic cell trafficking by chemokines. Springer Semin Immunopathol 22:345–369.

    PubMed  CAS  Google Scholar 

  • Chen, W. K., Chen, F. J., Zeng, Z. Y., Wu, G. H., Guo, Z. M., Wei, M. W., Yang, A. K., Zhang, Q., He, J. H. and Hou, J. H. 2005. [Expression and clinical significance of CD1a+ dendritic cells in glottic squamous cell carcinoma]. Ai Zheng 24:1124–1126.

    PubMed  CAS  Google Scholar 

  • Colasante, A., Castrilli, G., Aiello, F. B., Brunetti, M. and Musiani, P. 1995. Role of cytokines in distribution and differentiation of dendritic cell/Langerhans' cell lineage in human primary carcinomas of the lung. Hum Pathol 26:866–872.

    PubMed  CAS  Google Scholar 

  • Colasante, A., Poletti, V., Rosini, S., Ferracini, R. and Musiani, P. 1993. Langerhans cells in Langerhans cell histiocytosis and peripheral adenocarcinomas of the lung. Am Rev Respir Dis 148:752–759.

    PubMed  CAS  Google Scholar 

  • Coli, A., Bigotti, G. and Cione, T. 1990. Langerhans cell and HLA class II molecules distribution in lung carcinoma. J Nucl Med Allied Sci 34:185–189.

    PubMed  CAS  Google Scholar 

  • Coppola, D., Fu, L., Nicosia, S. V., Kounelis, S. and Jones, M. 1998. Prognostic significance of p53, bcl-2, vimentin, and S100 protein-positive Langerhans cells in endometrial carcinoma. Hum Pathol 29:455–462.

    PubMed  CAS  Google Scholar 

  • Coukos, G., Benencia, F., Buckanovich, R. J. and Conejo-Garcia, J. R. 2005. The role of dendritic cell precursors in tumour vasculogenesis. Br J Cancer 92:1182–1187.

    PubMed  CAS  Google Scholar 

  • Coventry, B. J., Lee, P. L., Gibbs, D. and Hart, D. N. 2002. Dendritic cell density and activation status in human breast cancer -- CD1a, CMRF-44, CMRF-56 and CD-83 expression. Br J Cancer 86:546–551.

    PubMed  CAS  Google Scholar 

  • Cox, K., North, M., Burke, M., Singhal, H., Renton, S., Aqel, N., Islam, S. and Knight, S. C. 2005. Plasmacytoid dendritic cells (PDC) are the major DC subset innately producing cytokines in human lymph nodes. J Leukoc Biol 78:1142–1152.

    PubMed  CAS  Google Scholar 

  • Cui, G., Yuan, A., Goll, R., Olsen, T., Husebekk, A., Vonen, B. and Florholmen, J. 2007. Distinct changes of dendritic cell number and IL-12 mRNA level in adjacent mucosa throughout the colorectal adenoma-carcinoma sequence. Cancer Immunol Immunother 56:1993–2001.

    PubMed  CAS  Google Scholar 

  • Dabrosin, C. 2005. Microdialysis - an in vivo technique for studies of growth factors in breast cancer. Front Biosci 10:1329–1335.

    PubMed  CAS  Google Scholar 

  • Dadabayev, A. R., Sandel, M. H., Menon, A. G., Morreau, H., Melief, C. J., Offringa, R., van der Burg, S. H., Janssen-van Rhijn, C., Ensink, N. G., Tollenaar, R. A., van de Velde, C. J. and Kuppen, P. J. 2004. Dendritic cells in colorectal cancer correlate with other tumor-infiltrating immune cells. Cancer Immunol Immunother 53:978–986.

    PubMed  CAS  Google Scholar 

  • Dallal, R. M., Christakos, P., Lee, K., Egawa, S., Son, Y. I. and Lotze, M. T. 2002. Paucity of dendritic cells in pancreatic cancer. Surgery 131:135–138.

    PubMed  Google Scholar 

  • de Vries, I. J., Lesterhuis, W. J., Barentsz, J. O., Verdijk, P., van Krieken, J. H., Boerman, O. C., Oyen, W. J., Bonenkamp, J. J., Boezeman, J. B., Adema, G. J., Bulte, J. W., Scheenen, T. W., Punt, C. J., Heerschap, A. and Figdor, C. G. 2005. Magnetic resonance tracking of dendritic cells in melanoma patients for monitoring of cellular therapy. Nat Biotechnol 23:1407–1413.

    PubMed  Google Scholar 

  • Dong, P., Li, X., Zhu, Z., Yu, Z., Lu, G., Sun, Z. and Wang, S. 2004. Application of tissue microarray: evaluation of the expression of S-100-positive dendritic cells, tumor suppressor gene p63 and tissue inhibitor of metalloproteinase-1 in laryngeal carcinoma. Acta Otolaryngol 124:1204–1207.

    PubMed  CAS  Google Scholar 

  • Esche, C., Lokshin, A., Shurin, G. V., Gastman, B. R., Rabinowich, H., Watkins, S. C., Lotze, M. T. and Shurin, M. R. 1999. Tumor's other immune targets: dendritic cells. J Leukoc Biol 66:336–344.

    PubMed  CAS  Google Scholar 

  • Espina, V., Wulfkuhle, J. D., Calvert, V. S., VanMeter, A., Zhou, W., Coukos, G., Geho, D. H., Petricoin, E. F., 3rd and Liotta, L. A. 2006. Laser-capture microdissection. Nat Protoc 1:586–603.

    PubMed  CAS  Google Scholar 

  • Fend, F., Kremer, M. and Quintanilla-Martinez, L. 2000. Laser capture microdissection: methodical aspects and applications with emphasis on immuno-laser capture microdissection. Pathobiology 68:209–214.

    PubMed  CAS  Google Scholar 

  • Frederick, M. J., Henderson, Y., Xu, X., Deavers, M. T., Sahin, A. A., Wu, H., Lewis, D. E., El-Naggar, A. K. and Clayman, G. L. 2000. In vivo expression of the novel CXC chemokine BRAK in normal and cancerous human tissue. Am J Pathol 156:1937–1950.

    PubMed  CAS  Google Scholar 

  • Fricke, I. and Gabrilovich, D. I. 2006. Dendritic cells and tumor microenvironment: a dangerous liaison. Immunol Invest 35:459–483.

    PubMed  CAS  Google Scholar 

  • Furihata, M., Ohtsuki, Y., Ido, E., Iwata, J., Sonobe, H., Araki, K., Ogoshi, S. and Ohmori, K. 1992. HLA-DR antigen- and S-100 protein-positive dendritic cells in esophageal squamous cell carcinoma--their distribution in relation to prognosis. Virchows Arch B Cell Pathol Incl Mol Pathol 61:409–414.

    PubMed  CAS  Google Scholar 

  • Furihata, M., Ono, Y., Ichikawa, K., Tomita, S., Fujimori, T. and Kubota, K. 2005. Prognostic significance of CD83 positive, mature dendritic cells in the gallbladder carcinoma. Oncol Rep 14:353–356.

    PubMed  CAS  Google Scholar 

  • Furumoto, K., Soares, L., Engleman, E. G. and Merad, M. 2004. Induction of potent antitumor immunity by in situ targeting of intratumoral DCs. J Clin Invest 113:774–783.

    PubMed  CAS  Google Scholar 

  • Gabrilovich, D. I., Corak, J., Ciernik, I. F., Kavanaugh, D. and Carbone, D. P. 1997. Decreased antigen presentation by dendritic cells in patients with breast cancer. Clin Cancer Res 3:483–490.

    PubMed  CAS  Google Scholar 

  • Gallo, O., Libonati, G. A., Gallina, E., Fini-Storchi, O., Giannini, A., Urso, C. and Bondi, R. 1991. Langerhans cells related to prognosis in patients with laryngeal carcinoma. Arch Otolaryngol Head Neck Surg 117:1007–1010.

    PubMed  CAS  Google Scholar 

  • Garcia-Plata, D., Lessana-Leibowitch, M., Palangie, A., Gulliemette, J., Sedel, D., Mendez, L. and Mozos, E. 1995. Immunophenotype analysis of dendritic cells and lymphocytes associated with cutaneous malignant melanomas. Invasion Metastasis 15:125–134.

    PubMed  CAS  Google Scholar 

  • Ghiringhelli, F., Apetoh, L., Housseau, F., Kroemer, G. and Zitvogel, L. 2007. Links between innate and cognate tumor immunity. Curr Opin Immunol 19:224–231.

    PubMed  CAS  Google Scholar 

  • Giannini, A., Bianchi, S., Messerini, L., Gallo, O., Gallina, E., Asprella Libonati, G., Olmi, P. and Zampi, G. 1991. Prognostic significance of accessory cells and lymphocytes in nasopharyngeal carcinoma. Pathol Res Pract 187:496–502.

    PubMed  CAS  Google Scholar 

  • Goldman, S. A., Baker, E., Weyant, R. J., Clarke, M. R., Myers, J. N. and Lotze, M. T. 1998. Peritumoral CD1a-positive dendritic cells are associated with improved survival in patients with tongue carcinoma. Arch Otolaryngol Head Neck Surg 124:641–646.

    PubMed  CAS  Google Scholar 

  • Gottfried, E., Kreutz, M., Haffner, S., Holler, E., Iacobelli, M., Andreesen, R. and Eissner, G. 2007. Differentiation of human tumour-associated dendritic cells into endothelial-like cells: an alternative pathway of tumour angiogenesis. Scand J Immunol 65:329–335.

    PubMed  CAS  Google Scholar 

  • Hashimoto, S. I., Suzuki, T., Nagai, S., Yamashita, T., Toyoda, N. and Matsushima, K. 2000. Identification of genes specifically expressed in human activated and mature dendritic cells through serial analysis of gene expression. Blood 96:2206–2214.

    PubMed  CAS  Google Scholar 

  • Hawthorn, R. J., Murdoch, J. B., MacLean, A. B. and MacKie, R. M. 1988. Langerhans' cells and subtypes of human papillomavirus in cervical intraepithelial neoplasia. BMJ 297:643–646.

    PubMed  CAS  Google Scholar 

  • Hayati, A. R. and Zulkarnaen, M. 2007. An immunohistochemical study of CD1a and CD83-positive infiltrating dendritic cell density in cervical neoplasia. Int J Gynecol Pathol 26:83–88.

    PubMed  Google Scholar 

  • Hillenbrand, E. E., Neville, A. M. and Coventry, B. J. 1999. Immunohistochemical localization of CD1a-positive putative dendritic cells in human breast tumours. Br J Cancer 79:940–944.

    PubMed  CAS  Google Scholar 

  • Honig, A., Schaller, N., Dietl, J., Backe, J. and Kammerer, U. 2005. S100 as an immunohistochemically-detected marker with prognostic significance in endometrial carcinoma. Anticancer Res 25:1747–1753.

    PubMed  CAS  Google Scholar 

  • Hromas, R., Broxmeyer, H. E., Kim, C., Nakshatri, H., Christopherson, K., 2nd, Azam, M. and Hou, Y. H. 1999. Cloning of BRAK, a novel divergent CXC chemokine preferentially expressed in normal versus malignant cells. Biochem Biophys Res Commun 255:703–706.

    PubMed  CAS  Google Scholar 

  • Huang, J., Tatsumi, T., Pizzoferrato, E., Vujanovic, N. and Storkus, W. J. 2005. Nitric oxide sensitizes tumor cells to dendritic cell-mediated apoptosis, uptake, and cross-presentation. Cancer Res 65:8461–8470.

    PubMed  CAS  Google Scholar 

  • Hubert, P., Caberg, J. H., Gilles, C., Bousarghin, L., Franzen-Detrooz, E., Boniver, J. and Delvenne, P. 2005. E-cadherin-dependent adhesion of dendritic and Langerhans cells to keratinocytes is defective in cervical human papillomavirus-associated (pre)neoplastic lesions. J Pathol 206:346–355.

    PubMed  CAS  Google Scholar 

  • Inoshima, N., Nakanishi, Y., Minami, T., Izumi, M., Takayama, K., Yoshino, I. and Hara, N. 2002. The influence of dendritic cell infiltration and vascular endothelial growth factor expression on the prognosis of non-small cell lung cancer. Clin Cancer Res 8:3480–3486.

    PubMed  CAS  Google Scholar 

  • Inoue, K., Furihata, M., Ohtsuki, Y. and Fujita, Y. 1993. Distribution of S-100 protein-positive dendritic cells and expression of HLA-DR antigen in transitional cell carcinoma of the urinary bladder in relation to tumour progression and prognosis. Virchows Arch A Pathol Anat Histopathol 422:351–355.

    PubMed  CAS  Google Scholar 

  • Inoue, Y., Nakayama, Y., Minagawa, N., Katsuki, T., Nagashima, N., Matsumoto, K., Shibao, K., Tsurudome, Y., Hirata, K., Nagata, N. and Itoh, H. 2005. Relationship between interleukin-12-expressing cells and antigen-presenting cells in patients with colorectal cancer. Anticancer Res 25:3541–3546.

    PubMed  CAS  Google Scholar 

  • Ioachim-Velogianni, E., Stavropoulos, N. E., Kitsiou, E., Stefanaki, S. and Agnantis, N. J. 1995. Distribution of CD1a-positive Langerhans cells and lymphocyte subsets in transitional cell carcinoma of the urinary bladder. An immunohistological study on frozen sections. J Pathol 177:401–406.

    PubMed  CAS  Google Scholar 

  • Ishigami, S., Natsugoe, S., Matsumoto, M., Okumura, H., Sakita, H., Nakashima, S., Takao, S. and Aikou, T. 2003. Clinical implications of intratumoral dendritic cell infiltration in esophageal squamous cell carcinoma. Oncol Rep 10:1237–1240.

    PubMed  Google Scholar 

  • Ishigami, S., Natsugoe, S., Tokuda, K., Nakajo, A., Xiangming, C., Iwashige, H., Aridome, K., Hokita, S. and Aikou, T. 2000. Clinical impact of intratumoral natural killer cell and dendritic cell infiltration in gastric cancer. Cancer Lett 159:103–108.

    PubMed  CAS  Google Scholar 

  • Iwamoto, M., Shinohara, H., Miyamoto, A., Okuzawa, M., Mabuchi, H., Nohara, T., Gon, G., Toyoda, M. and Tanigawa, N. 2003. Prognostic value of tumor-infiltrating dendritic cells expressing CD83 in human breast carcinomas. Int J Cancer 104:92–97.

    PubMed  CAS  Google Scholar 

  • Jimenez-Flores, R., Mendez-Cruz, R., Ojeda-Ortiz, J., Munoz-Molina, R., Balderas-Carrillo, O., de la Luz Diaz-Soberanes, M., Lebecque, S., Saeland, S., Daneri-Navarro, A., Garcia-Carranca, A., Ullrich, S. E. and Flores-Romo, L. 2006. High-risk human papilloma virus infection decreases the frequency of dendritic Langerhans' cells in the human female genital tract. Immunology 117:220–228.

    PubMed  CAS  Google Scholar 

  • Karakok, M., Bayazit, Y. A., Ucak, R., Ozer, E., Kanlikama, M., Mumbuc, S. and Sari, I. 2003. Langerhans cell related inflammatory reaction in laryngeal squamous cell carcinoma. Auris Nasus Larynx 30:81–84.

    PubMed  Google Scholar 

  • Katsenelson, N. S., Shurin, G. V., Bykovskaia, S. N., Shogan, J. and Shurin, M. R. 2001. Human small cell lung carcinoma and carcinoid tumor regulate dendritic cell maturation and function. Mod Pathol 14:40–45.

    PubMed  CAS  Google Scholar 

  • Kikuchi, K., Kusama, K., Sano, M., Nakanishi, Y., Ishige, T., Ohni, S., Oinuma, T. and Nemoto, N. 2006. Vascular endothelial growth factor and dendritic cells in human squamous cell carcinoma of the oral cavity. Anticancer Res 26:1833–1848.

    PubMed  CAS  Google Scholar 

  • Kikuchi, K., Kusama, K., Taguchi, K., Ishikawa, F., Okamoto, M., Shimada, J., Sakashita, H. and Yamamo, Y. 2002. Dendritic cells in human squamous cell carcinoma of the oral cavity. Anticancer Res 22:545–557.

    PubMed  CAS  Google Scholar 

  • Kobayashi, M., Suzuki, K., Yashi, M., Yuzawa, M., Takayashiki, N. and Morita, T. 2007. Tumor infiltrating dendritic cells predict treatment response to immunotherapy in patients with metastatic renal cell carcinoma. Anticancer Res 27:1137–1141.

    PubMed  CAS  Google Scholar 

  • Kurabayashi, A., Furihata, M., Matsumoto, M., Hayashi, H. and Ohtsuki, Y. 2004. Distribution of tumor-infiltrating dendritic cells in human non-small cell lung carcinoma in relation to apoptosis. Pathol Int 54:302–310.

    PubMed  Google Scholar 

  • Kurihara, K. and Hashimoto, N. 1985. The pathological significance of Langerhans cells in oral cancer. J Oral Pathol 14:289–298.

    PubMed  CAS  Google Scholar 

  • Ladanyi, A., Kiss, J., Somlai, B., Gilde, K., Fejos, Z., Mohos, A., Gaudi, I. and Timar, J. 2007. Density of DC–LAMP(+) mature dendritic cells in combination with activated T lymphocytes infiltrating primary cutaneous melanoma is a strong independent prognostic factor. Cancer Immunol Immunother 56:1459–1469.

    PubMed  Google Scholar 

  • Lauriola, L., Michetti, F., Sentinelli, S. and Cocchia, D. 1984. Detection of S-100 labelled cells in nasopharyngeal carcinoma. J Clin Pathol 37:1235–1238.

    PubMed  CAS  Google Scholar 

  • Lespagnard, L., Gancberg, D., Rouas, G., Leclercq, G., de Saint-Aubain Somerhausen, N., Di Leo, A., Piccart, M., Verhest, A. and Larsimont, D. 1999. Tumor-infiltrating dendritic cells in adenocarcinomas of the breast: a study of 143 neoplasms with a correlation to usual prognostic factors and to clinical outcome. Int J Cancer 84:309–314.

    PubMed  CAS  Google Scholar 

  • Levi, G., Feldman, J., Holman, S., Salarieh, A., Strickler, H. D., Alter, S. and Minkoff, H. 2005. Relationship between HIV viral load and Langerhans cells of the cervical epithelium. J Obstet Gynaecol Res 31:178–184.

    PubMed  Google Scholar 

  • Ma, C. X., Jia, T. C., Li, X. R., Zhand, Z. F. and Yiao, C. B. 1995. Langerhans cells in nasopharyngeal carcinoma in relation to prognosis. In Vivo 9:225–229.

    PubMed  CAS  Google Scholar 

  • Makarenkova, V. P., Shurin, G. V., Tourkova, I. L., Balkir, L., Pirtskhalaishvili, G., Perez, L., Gerein, V., Siegfried, J. M. and Shurin, M. R. 2003. Lung cancer-derived bombesin-like peptides down-regulate the generation and function of human dendritic cells. J Neuroimmunol 145:55–67.

    PubMed  CAS  Google Scholar 

  • Manna, P. P. and Mohanakumar, T. 2002. Human dendritic cell mediated cytotoxicity against breast carcinoma cells in vitro. J Leukoc Biol 72:312–320.

    PubMed  CAS  Google Scholar 

  • Matsuda, H., Mori, M., Tsujitani, S., Ohno, S., Kuwano, H. and Sugimachi, K. 1990. Immunohistochemical evaluation of squamous cell carcinoma antigen and S-100 protein-positive cells in human malignant esophageal tissues. Cancer 65:2261–2265.

    PubMed  CAS  Google Scholar 

  • McArdle, J. P. and Muller, H. K. 1986. Quantitative assessment of Langerhans' cells in human cervical intraepithelial neoplasia and wart virus infection. Am J Obstet Gynecol 154:509–515.

    PubMed  CAS  Google Scholar 

  • Miyagawa, S., Soeda, J., Takagi, S., Miwa, S., Ichikawa, E. and Noike, T. 2004. Prognostic significance of mature dendritic cells and factors associated with their accumulation in metastatic liver tumors from colorectal cancer. Hum Pathol 35:1392–1396.

    PubMed  Google Scholar 

  • Nagorsen, D., Voigt, S., Berg, E., Stein, H., Thiel, E. and Loddenkemper, C. 2007. Tumor-infiltrating macrophages and dendritic cells in human colorectal cancer: relation to local regulatory T cells, systemic T-cell response against tumor-associated antigens and survival. J Transl Med 5:62.

    PubMed  Google Scholar 

  • Nakajima, T., Kodama, T., Tsumuraya, M., Shimosato, Y. and Kameya, T. 1985. S-100 protein-positive Langerhans cells in various human lung cancers, especially in peripheral adenocarcinomas. Virchows Arch A Pathol Anat Histopathol 407:177–189.

    PubMed  CAS  Google Scholar 

  • Nakakubo, Y., Miyamoto, M., Cho, Y., Hida, Y., Oshikiri, T., Suzuoki, M., Hiraoka, K., Itoh, T., Kondo, S. and Katoh, H. 2003. Clinical significance of immune cell infiltration within gallbladder cancer. Br J Cancer 89:1736–1742.

    PubMed  CAS  Google Scholar 

  • Nakayama, Y., Inoue, Y., Minagawa, N., Katsuki, T., Nagashima, N., Onitsuka, K., Tsurudome, Y., Sako, T., Hirata, K., Nagata, N. and Itoh, H. 2003. Relationships between S-100 protein-positive cells and clinicopathological factors in patients with colorectal cancer. Anticancer Res 23:4423–4426.

    PubMed  CAS  Google Scholar 

  • Nicolas, A., Cathelin, D., Larmonier, N., Fraszczak, J., Puig, P. E., Bouchot, A., Bateman, A., Solary, E. and Bonnotte, B. 2007. Dendritic cells trigger tumor cell death by a nitric oxide-dependent mechanism. J Immunol 179:812–818.

    PubMed  CAS  Google Scholar 

  • O'Donnell, R. K., Mick, R., Feldman, M., Hino, S., Wang, Y., Brose, M. S. and Muschel, R. J. 2007. Distribution of dendritic cell subtypes in primary oral squamous cell carcinoma is inconsistent with a functional response. Cancer Lett 255:145–152.

    PubMed  Google Scholar 

  • Perrot, I., Blanchard, D., Freymond, N., Isaac, S., Guibert, B., Pacheco, Y. and Lebecque, S. 2007. Dendritic cells infiltrating human non-small cell lung cancer are blocked at immature stage. J Immunol 178:2763–2769.

    PubMed  CAS  Google Scholar 

  • Pirtskhalaishvili, G., Shurin, G. V., Esche, C., Trump, D. L. and Shurin, M. R. 2001. TNF-alpha protects dendritic cells from prostate cancer-induced apoptosis. Prostate Cancer Prostatic Dis 4:221–227.

    PubMed  CAS  Google Scholar 

  • Reichert, T. E., Scheuer, C., Day, R., Wagner, W. and Whiteside, T. L. 2001. The number of intratumoral dendritic cells and zeta-chain expression in T cells as prognostic and survival biomarkers in patients with oral carcinoma. Cancer 91:2136–2147.

    PubMed  CAS  Google Scholar 

  • Saito, H., Tsujitani, S., Ikeguchi, M., Maeta, M. and Kaibara, N. 1998. Relationship between the expression of vascular endothelial growth factor and the density of dendritic cells in gastric adenocarcinoma tissue. Br J Cancer 78:1573–1577.

    PubMed  CAS  Google Scholar 

  • Sandel, M. H., Dadabayev, A. R., Menon, A. G., Morreau, H., Melief, C. J., Offringa, R., van der Burg, S. H., Janssen-van Rhijn, C. M., Ensink, N. G., Tollenaar, R. A., van de Velde, C. J. and Kuppen, P. J. 2005. Prognostic value of tumor-infiltrating dendritic cells in colorectal cancer: role of maturation status and intratumoral localization. Clin Cancer Res 11:2576–2582.

    PubMed  CAS  Google Scholar 

  • Schaerli, P., Willimann, K., Ebert, L. M., Walz, A. and Moser, B. 2005. Cutaneous CXCL14 targets blood precursors to epidermal niches for Langerhans cell differentiation. Immunity 23:331–342.

    PubMed  CAS  Google Scholar 

  • Schwaab, T., Schned, A. R., Heaney, J. A., Cole, B. F., Atzpodien, J., Wittke, F. and Ernstoff, M. S. 1999. In vivo description of dendritic cells in human renal cell carcinoma. J Urol 162:567–573.

    PubMed  CAS  Google Scholar 

  • Schwaab, T., Weiss, J. E., Schned, A. R. and Barth Jr, R. J. 2001. Dendritic cell infiltration in colon cancer. J Immunother 24:130–137.

    CAS  Google Scholar 

  • Shellenberger, T. D., Wang, M., Gujrati, M., Jayakumar, A., Strieter, R. M., Burdick, M. D., Ioannides, C. G., Efferson, C. L., El-Naggar, A. K., Roberts, D., Clayman, G. L. and Frederick, M. J. 2004. BRAK/CXCL14 is a potent inhibitor of angiogenesis and a chemotactic factor for immature dendritic cells. Cancer Res 64:8262–8270.

    PubMed  CAS  Google Scholar 

  • Shurin, G. V., Ferris, R. L., Tourkova, I. L., Perez, L., Lokshin, A., Balkir, L., Collins, B., Chatta, G. S. and Shurin, M. R. 2005. Loss of new chemokine CXCL14 in tumor tissue is associated with low infiltration by dendritic cells (DC), while restoration of human CXCL14 expression in tumor cells causes attraction of DC both in vitro and in vivo. J Immunol 174:5490–5498.

    PubMed  CAS  Google Scholar 

  • Shurin, G. V., Shurin, M. R., Bykovskaia, S., Shogan, J., Lotze, M. T. and Barksdale, E. M., Jr. 2001. Neuroblastoma-derived gangliosides inhibit dendritic cell generation and function. Cancer Res 61:363–369.

    PubMed  CAS  Google Scholar 

  • Shurin, M. R., Shurin, G. V., Lokshin, A., Yurkovetsky, Z. R., Gutkin, D. W., Chatta, G., Zhong, H., Han, B. and Ferris, R. L. 2006. Intratumoral cytokines/chemokines/growth factors and tumor infiltrating dendritic cells: friends or enemies? Cancer Metastasis Rev 25:333–356.

    PubMed  CAS  Google Scholar 

  • Simonetti, O., Goteri, G., Lucarini, G., Rubini, C., Stramazzotti, D., Lo Muzio, L., Biagini, G. and Offidani, A. 2007. In melanoma changes of immature and mature dendritic cell expression correlate with tumor thickness: an immunohistochemical study. Int J Immunopathol Pharmacol 20:325–333.

    PubMed  CAS  Google Scholar 

  • Stene, M. A., Babajanians, M., Bhuta, S. and Cochran, A. J. 1988. Quantitative alterations in cutaneous Langerhans cells during the evolution of malignant melanoma of the skin. J Invest Dermatol 91:125–128.

    PubMed  CAS  Google Scholar 

  • Strauss, L., Volland, D., Kunkel, M. and Reichert, T. E. 2005. Dual role of VEGF family members in the pathogenesis of head and neck cancer (HNSCC): possible link between angiogenesis and immune tolerance. Med Sci Monit 11:BR280–292.

    PubMed  CAS  Google Scholar 

  • Suzuki, A., Masuda, A., Nagata, H., Kameoka, S., Kikawada, Y., Yamakawa, M. and Kasajima, T. 2002. Mature dendritic cells make clusters with T cells in the invasive margin of colorectal carcinoma. J Pathol 196:37–43.

    PubMed  Google Scholar 

  • Takagi, S., Miyagawa, S., Ichikawa, E., Soeda, J., Miwa, S., Miyagawa, Y., Iijima, S., Noike, T., Kobayashi, A. and Kawasaki, S. 2004. Dendritic cells, T-cell infiltration, and Grp94 expression in cholangiocellular carcinoma. Hum Pathol 35:881–886.

    PubMed  CAS  Google Scholar 

  • Takahashi, A., Kono, K., Itakura, J., Amemiya, H., Feng Tang, R., Iizuka, H., Fujii, H. and Matsumoto, Y. 2002. Correlation of vascular endothelial growth factor-C expression with tumor-infiltrating dendritic cells in gastric cancer. Oncology 62:121–127.

    PubMed  CAS  Google Scholar 

  • Toriyama, K., Wen, D. R., Paul, E. and Cochran, A. J. 1993. Variations in the distribution, frequency, and phenotype of Langerhans cells during the evolution of malignant melanoma of the skin. J Invest Dermatol 100:269S–273S.

    PubMed  CAS  Google Scholar 

  • Treilleux, I., Blay, J. Y., Bendriss-Vermare, N., Ray-Coquard, I., Bachelot, T., Guastalla, J. P., Bremond, A., Goddard, S., Pin, J. J., Barthelemy-Dubois, C. and Lebecque, S. 2004. Dendritic cell infiltration and prognosis of early stage breast cancer. Clin Cancer Res 10:7466–7474.

    PubMed  CAS  Google Scholar 

  • Troy, A., Davidson, P., Atkinson, C. and Hart, D. 1998a. Phenotypic characterisation of the dendritic cell infiltrate in prostate cancer. J Urol 160:214–219.

    PubMed  CAS  Google Scholar 

  • Troy, A. J., Davidson, P. J., Atkinson, C. H. and Hart, D. N. 1999. CD1a dendritic cells predominate in transitional cell carcinoma of bladder and kidney but are minimally activated. J Urol 161:1962–1967.

    PubMed  CAS  Google Scholar 

  • Troy, A. J., Summers, K. L., Davidson, P. J., Atkinson, C. H. and Hart, D. N. 1998b. Minimal recruitment and activation of dendritic cells within renal cell carcinoma. Clin Cancer Res 4:585–593.

    PubMed  CAS  Google Scholar 

  • Tsuge, K., Takeda, H., Kawada, S., Maeda, K. and Yamakawa, M. 2005. Characterization of dendritic cells in differentiated thyroid cancer. J Pathol 205:565–576.

    PubMed  CAS  Google Scholar 

  • Tsujitani, S., Furukawa, T., Tamada, R., Okamura, T., Yasumoto, K. and Sugimachi, K. 1987. Langerhans cells and prognosis in patients with gastric carcinoma. Cancer 59:501–505.

    PubMed  CAS  Google Scholar 

  • Tsujitani, S., Kakeji, Y., Maehara, Y., Sugimachi, K. and Kaibara, N. 1993. Dendritic cells prevent lymph node metastasis in patients with gastric cancer. In Vivo 7:233–237.

    PubMed  CAS  Google Scholar 

  • Tsujitani, S., Kakeji, Y., Watanabe, A., Kohnoe, S., Maehara, Y. and Sugimaghi, K. 1992. Infiltration of S-100 protein positive dendritic cells and peritoneal recurrence in advanced gastric cancer. Int Surg 77:238–241.

    PubMed  CAS  Google Scholar 

  • Tsukayama, S., Omura, K., Yoshida, K., Tanaka, Y. and Watanabe, G. 2005. Prognostic value of CD83-positive mature dendritic cells and their relation to vascular endothelial growth factor in advanced human gastric cancer. Oncol Rep 14:369–375.

    PubMed  CAS  Google Scholar 

  • Ugolini, C., Basolo, F., Proietti, A., Vitti, P., Elisei, R., Miccoli, P. and Toniolo, A. 2007. Lymphocyte and immature dendritic cell infiltrates in differentiated, poorly differentiated, and undifferentiated thyroid carcinoma. Thyroid 17:389–393.

    PubMed  Google Scholar 

  • Vakkila, J., Jaffe, R., Michelow, M. and Lotze, M. T. 2006. Pediatric cancers are infiltrated predominantly by macrophages and contain a paucity of dendritic cells: a major nosologic difference with adult tumors. Clin Cancer Res 12:2049–2054.

    PubMed  CAS  Google Scholar 

  • Vermi, W., Bonecchi, R., Facchetti, F., Bianchi, D., Sozzani, S., Festa, S., Berenzi, A., Cella, M. and Colonna, M. 2003. Recruitment of immature plasmacytoid dendritic cells (plasmacytoid monocytes) and myeloid dendritic cells in primary cutaneous melanomas. J Pathol 200:255–268.

    PubMed  Google Scholar 

  • Vicari, A. P., Treilleux, I. and Lebecque, S. 2004. Regulation of the trafficking of tumour-infiltrating dendritic cells by chemokines. Semin Cancer Biol 14:161–169.

    PubMed  CAS  Google Scholar 

  • Whiteside, T. L. 2006. The role of immune cells in the tumor microenvironment. Cancer Treat Res 130:103–124.

    PubMed  CAS  Google Scholar 

  • Yamakawa, M., Yamada, K., Orui, H., Tsuge, T., Ogata, T., Dobashi, M. and Imai, Y. 1995. Immunohistochemical analysis of dendritic/Langerhans cells in thyroid carcinomas. Anal Cell Pathol 8:331–343.

    PubMed  CAS  Google Scholar 

  • Yin, X. Y., Lu, M. D., Lai, Y. R., Liang, L. J. and Huang, J. F. 2003. Prognostic significances of tumor-infiltrating S-100 positive dendritic cells and lymphocytes in patients with hepatocellular carcinoma. Hepatogastroenterology 50:1281–1284.

    PubMed  Google Scholar 

  • Zeid, N. A. and Muller, H. K. 1993. S100 positive dendritic cells in human lung tumors associated with cell differentiation and enhanced survival. Pathology 25:338–343.

    PubMed  CAS  Google Scholar 

  • Zhong, H., Han, B., Tourkova, I. L., Lokshin, A., Rosenbloom, A., Shurin, M. R. and Shurin, G. V. 2007. Low-dose Paclitaxel prior to intratumoral dendritic cell vaccine modulates intratumoral cytokine network and lung cancer growth. Clin Cancer Res 13:5455–5462.

    PubMed  CAS  Google Scholar 

  • Zijlmans, H. J., Fleuren, G. J., Baelde, H. J., Eilers, P. H., Kenter, G. G. and Gorter, A. 2007. Role of tumor-derived proinflammatory cytokines GM-CSF, TNF-alpha, and IL-12 in the migration and differentiation of antigen-presenting cells in cervical carcinoma. Cancer 109:556–565.

    PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Program Leader, Pathology and Lab Medicine, VAMC Pittsburgh, University Drive C, 132L-U, Pittsburgh, PA 15240, USA

    Dmitry W. Gutkin

Authors
  1. Dmitry W. Gutkin
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Dmitry W. Gutkin .

Editor information

Editors and Affiliations

    Rights and permissions

    Reprints and permissions

    Copyright information

    © 2009 Springer Science+Business Media, LLC

    About this chapter

    Cite this chapter

    Gutkin, D.W. (2009). Tumor-Infiltrating Dendritic Cells: The Pathologist’s Perspective. In: Salter, R., Shurin, M. (eds) Dendritic Cells in Cancer. Springer, New York, NY. https://doi.org/10.1007/978-0-387-88611-4_3

    Download citation

    Publish with us

    Policies and ethics

    Search

    Navigation