Skip to main content
SpringerLink
Log in
Book cover

MicroRNA and Cancer pp 67–74Cite as

MicroRNAs Reprogram Tumor Immune Response

  • Protocol
  • First Online:

Part of the book series: Methods in Molecular Biology ((MIMB,volume 1699))

Abstract

Endogenously produced microRNAs (miRNAs) are predicted to regulate the translation of over two-thirds all human gene transcripts. Certain microRNAs regulate expression of genes that are critically involved in both innate and adaptive immune responses. miRNAs have been demonstrated to function as crucial regulators of immune response under both physiological and pathological conditions. Specifically, different miRNAs have been reported to have a role in controlling the development and the functions of tumor-associated immune cells. Immune cells represent a highly attractive target for microRNA gene therapy approaches, as these cells can be isolated, treated, and then reintroduced into patients. In this chapter, we will discuss how recent discoveries on the roles of microRNAs in immune-regulation will advance the field of cancer immunology and immunotherapy.

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

Protocol
USD   49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   159.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
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

Learn about institutional subscriptions

Springer Nature is developing a new tool to find and evaluate Protocols. Learn more

References

  1. Ehrlich P (1909) Über den jetzigen stand der karzinomforschung. Ned Tijdschr Geneeskd 5:273–290

    Google Scholar 

  2. Stratton MR, Campbell PJ, Futreal PA (2009) The cancer genome. Nature 458:719–724

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Hanahan D, Weinberg RA (2011) Hallmarks of cancer: the next generation. Cell 144:646–674

    Article  CAS  PubMed  Google Scholar 

  4. Tomasetti C, Vogelstein B (2015) Cancer etiology. Variation in cancer risk among tissues can be explained by the number of stem cell divisions. Science 347:78–81

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Burnet M (1970) The concept of immunologic surveillance. Prog ExpTumor Res 13:1–27

    Article  CAS  Google Scholar 

  6. Dunn GP, Old LJ, Schreiber RD (2004) The immunobiology of cancer immunosurveillance and immunoediting. Immunity 21:137–148

    Article  CAS  PubMed  Google Scholar 

  7. Gaudin C, Kremer F, Angevin E, Scott V, Triebel F (1999) A hsp70-2 mutation recognized by CTL on a human renal cell carcinoma. J Immunol 162:1730–1738

    CAS  PubMed  Google Scholar 

  8. Kawakami Y, Wang X, Shofuda T, Sumimoto H, Tupesis J, Fitzgerald E, Rosenberg S (2001) Isolation of a new melanoma antigen, MART-2, containing a mutated epitope recognized by autologous tumor-infiltrating T lymphocytes. J Immunol 166:2871–2877

    Article  CAS  PubMed  Google Scholar 

  9. Linard B, Bezieau S, Benlalam H, Labarriere N, Guilloux Y, Diez E, Jotereau F (2002) A ras-mutated peptide targeted by CTL infiltrating a human melanoma lesion. J Immunol 168:4802–4808

    Article  CAS  PubMed  Google Scholar 

  10. Huang J, El-Gamil M, Dudley ME, Li YF, Rosenberg SA, Robbins PF (2004) T cells associated with tumor regression recognize frameshifted products of the CDKN2A tumor suppressor gene locus and a mutated HLA class I gene product. J Immunol 172:6057–6064

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Lu YC, Robbins PF (2016) Targeting neoantigens for cancer immunotherapy. Int Immunol 28(7):365–370

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  12. Anagnostou V, Smith KN, Forde PM, Niknafs N, Bhattacharya R, White J, Zhang T, Adleff V, Phallen J, Wali N et al (2016) Evolution of neoantigen landscape during immune checkpoint blockade in non-small cell lung cancer. Cancer Discov 7(3):264–276

    Article  PubMed  Google Scholar 

  13. Freeman GJ, Long AJ, Iwai Y, Bourque K, Chernova T, Nishimura H, Fitz LJ, Malenkovich N, Okazaki T, Byrne MC et al (2000) Engagement of the PD-1 immunoinhibitory receptor by a novel B7 family member leads to negative regulation of lymphocyte activation. J Exp Med 192:1027–1034

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Hodi FS, O’Day SJ, McDermott DF, Weber RW, Sosman JA, Haanen JB, Gonzalez R, Robert C, Schadendorf D, Hassel JC et al (2010) Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med 363:711–723

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  15. Brahmer JR, Tykodi SS, Chow LQ, Hwu WJ, Topalian SL, Hwu P, Drake CG, Camacho LH, Kauh J, Odunsi K et al (2012) Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med 366:2455–2465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Powles T, Eder JP, Fine GD, Braiteh FS, Loriot Y, Cruz C, Bellmunt J, Burris HA, Petrylak DP, Teng SL et al (2014) MPDL3280A (anti-PD-L1) treatment leads to clinical activity in metastatic bladder cancer. Nature 515:558–562

    Article  CAS  PubMed  Google Scholar 

  17. Principe S, Hui AB, Bruce J, Sinha A, Liu FF, Kislinger T (2013) Tumor-derived exosomes and microvesicles in head and neck cancer: implications for tumor biology and biomarker discovery. Proteomics 13:1608–1623

    Article  CAS  PubMed  Google Scholar 

  18. Thakur BK, Zhang H, Becker A, Matei I, Huang Y, Costa-Silva B, Zheng Y, Hoshino A, Brazier H, Xiang J et al (2014) Double-stranded DNA in exosomes: a novel biomarker in cancer detection. Cell Res 24:766–769

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Kato M, Slack FJ (2008) microRNAs: small molecules with big roles—C. elegans to human cancer. Biol Cell 100:71–81

    Article  CAS  PubMed  Google Scholar 

  20. Lee RC, Feinbaum RL, Ambros V (1993) The C. elegans heterochronic gene lin-4 encodes small RNAs with antisense complementarity to lin-14. Cell 75:843–854

    Article  CAS  PubMed  Google Scholar 

  21. Reinhart BJ, Slack FJ, Basson M, Pasquinelli AE, Bettinger JC, Rougvie AE, Horvitz HR, Ruvkun G (2000) The 21-nucleotide let-7 RNA regulates developmental timing in Caenorhabditis elegans. Nature 403:901–906

    Article  CAS  PubMed  Google Scholar 

  22. Lagos-Quintana M, Rauhut R, Lendeckel W, Tuschl T (2001) Identification of novel genes coding for small expressed RNAs. Science 294:853–858

    Article  CAS  PubMed  Google Scholar 

  23. Lau NC, Lim LP, Weinstein EG, Bartel DP (2001) An abundant class of tiny RNAs with probable regulatory roles in Caenorhabditis elegans. Science 294:858–862

    Article  CAS  PubMed  Google Scholar 

  24. Lee RC, Ambros V (2001) An extensive class of small RNAs in Caenorhabditis elegans. Science 294:862–864

    Article  CAS  PubMed  Google Scholar 

  25. Bartel DP (2004) MicroRNAs: genomics, biogenesis, mechanism, and function. Cell 116:281–297

    Article  CAS  PubMed  Google Scholar 

  26. Kim VN, Nam JW (2006) Genomics of microRNA. Trends Genet 22(3):165–173

    Article  CAS  PubMed  Google Scholar 

  27. Hutvagner G, Zamore PD (2002) A microRNA in a multiple-turnover RNAi enzyme complex. Science 297:2056–2060

    Article  CAS  PubMed  Google Scholar 

  28. Wu W, Sun M, Zou GM, Chen J (2007) MicroRNA and cancer: current status and prospective. Int J Cancer 120(5):953–960

    Article  CAS  PubMed  Google Scholar 

  29. He L, Thomson JM, Hemann MT, Hernando-Monge E, Mu D, Goodson S, Powers S, Cordon-Cardo C, Lowe SW, Hannon GJ, Hammond SM (2005) A microRNA polycistron as a potential human oncogene. Nature 435:828–833

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. O’Donnell KA, Wentzel EA, Zeller KI, Dang CV, Mendell JT (2005) c-Myc-regulated microRNAs modulate E2F1 expression. Nature 435:839–843

    Article  PubMed  Google Scholar 

  31. Zhu S, Wu H, Wu F, Nie D, Sheng S, Mo YY (2008) MicroRNA-21 targets tumor suppressor genes in invasion and metastasis. Cell Res 18:350–359

    Article  CAS  PubMed  Google Scholar 

  32. Hua Z, Lv Q, Ye W, Wong CK, Cai G, Gu D, Ji Y, Zhao C, Wang J, Yang BB, Zhang Y (2006) MiRNA-directed regulation of VEGF and other angiogenic factors under hypoxia. PLoS One 1:e116

    Article  PubMed  PubMed Central  Google Scholar 

  33. Yu F, Yao H, Zhu P, Zhang X, Pan Q, Gong C, Huang Y, Hu X, Su F, Lieberman J (2007) Song E: let-7 regulates self renewal and tumorigenicity of breast cancer cells. Cell 131:1109–1123

    Article  CAS  PubMed  Google Scholar 

  34. Cobb BS, Nesterova TB, Thompson E, Hertweck A, O’Connor E, Godwin J, Wilson CB, Brockdorff N, Fisher AG, Smale ST, Merkenschlager M (2005) T cell lineage choice and differentiation in the absence of the RNase III enzyme Dicer. J Exp Med 201:1367–1373

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Okada H, Kohanbash G, Lotze MT (2010) MicroRNAs in immune regulation—opportunities for cancer immunotherapy. Int J Biochem Cell Biol 42:1256–1261

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Rodriguez A, Vigorito E, Clare S, Warren MV, Couttet P, Soond DR, van Dongen S, Grocock RJ, Das PP, Miska EA et al (2007) Requirement of bic/microRNA-155 for normal immune function. Science 316:608–611

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Paladini L, Fabris L, Bottai G, Raschioni C, Calin GA, Santarpia L (2016) Targeting microRNAs as key modulators of tumor immune response. J Exp Clin Cancer Res 35:103

    Article  PubMed  PubMed Central  Google Scholar 

  38. Suzuki HI, Katsura A, Matsuyama H, Miyazono K (2015) MicroRNA regulons in tumor microenvironment. Oncogene 34:3085–3094

    Article  CAS  PubMed  Google Scholar 

  39. Graff JW, Dickson AM, Clay G, McCaffrey AP, Wilson ME (2012) Identifying functional microRNAs in macrophages with polarized phenotypes. J Biol Chem 287:21816–21825

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Li L, Zhang J, Diao W, Wang D, Wei Y, Zhang CY, Zen K (2014) MicroRNA-155 and MicroRNA-21 promote the expansion of functional myeloid-derived suppressor cells. J Immunol 192:1034–1043

    Article  CAS  PubMed  Google Scholar 

  41. Gaziel-Sovran A, Segura MF, Di Micco R, Collins MK, Hanniford D, Vega-Saenz de Miera E, Rakus JF, Dankert JF, Shang S, Kerbel RS et al (2011) miR-30b/30d regulation of GalNAc transferases enhances invasion and immunosuppression during metastasis. Cancer Cell 20:104–118

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. Liu X, Robinson SN, Setoyama T, Tung SS, D'Abundo L, Shah MY, Yang H, Yvon E, Shah N, Yang H et al (2014) FOXP3 is a direct target of miR15a/16 in umbilical cord blood regulatory T cells. Bone Marrow Transplant 49:793–799

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Bezman NA, Chakraborty T, Bender T, Lanier LL (2011) miR-150 regulates the development of NK and iNKT cells. J Exp Med 208:2717–2731

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  44. Trotta R, Chen L, Ciarlariello D, Josyula S, Mao C, Costinean S, Yu L, Butchar JP, Tridandapani S, Croce CM, Caligiuri MA (2012) miR-155 regulates IFN-gamma production in natural killer cells. Blood 119:3478–3485

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  45. Matsuyama H, Suzuki HI, Nishimori H, Noguchi M, Yao T, Komatsu N, Mano H, Sugimoto K, Miyazono K (2011) miR-135b mediates NPM-ALK-driven oncogenicity and renders IL-17-producing immunophenotype to anaplastic large cell lymphoma. Blood 118:6881–6892

    Article  CAS  PubMed  Google Scholar 

  46. Smallwood DT, Apollonio B, Willimott S, Lezina L, Alharthi A, Ambrose AR, De Rossi G, Ramsay AG, Wagner SD (2016) Extracellular vesicles released by CD40/IL-4-stimulated CLL cells confer altered functional properties to CD4+ T cells. Blood 128:542–552

    Article  CAS  PubMed  Google Scholar 

  47. Xu S, Tao Z, Hai B, Liang H, Shi Y, Wang T, Song W, Chen Y, OuYang J, Chen J et al (2016) miR-424(322) reverses chemoresistance via T-cell immune response activation by blocking the PD-L1 immune checkpoint. Nat Commun 7:11406

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Cho JS, Kook SH, Robinson AR, Niedernhofer LJ, Lee BC (2013) Cell autonomous and nonautonomous mechanisms drive hematopoietic stem/progenitor cell loss in the absence of DNA repair. Stem Cells 31:511–525

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Sharma P, Allison JP (2015) The future of immune checkpoint therapy. Science 348:56–61

    Article  CAS  PubMed  Google Scholar 

  50. Cha E, Klinger M, Hou Y, Cummings C, Ribas A, Faham M, Fong L (2014) Improved survival with T cell clonotype stability after anti-CTLA-4 treatment in cancer patients. Sci Transl Med 6:238ra270

    Article  Google Scholar 

  51. Rizvi NA, Hellmann MD, Snyder A, Kvistborg P, Makarov V, Havel JJ, Lee W, Yuan J, Wong P, Ho TS et al (2015) Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science 348:124–128

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Zhang Y, Yang P, Sun T, Li D, Xu X, Rui Y, Li C, Chong M, Ibrahim T, Mercatali L et al (2013) miR-126 and miR-126* repress recruitment of mesenchymal stem cells and inflammatory monocytes to inhibit breast cancer metastasis. Nat Cell Biol 15:284–294

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Chou J, Lin JH, Brenot A, Kim JW, Provot S, Werb Z (2013) GATA3 suppresses metastasis and modulates the tumour microenvironment by regulating microRNA-29b expression. Nat Cell Biol 15:201–213

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Translational Medical Center, Zhengzhou Central Hospital, Affiliated to Zhengzhou University, 195 Tongbai Road, Zhengzhou, 450007, People’s Republic of China

    Wei Cao

  2. Department of Gastroenterology, The First Affiliated Hospital of Nanjing Medical University, Nanjing, 210029, Jiangsu Province, China

    Wenfang Cheng

  3. Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California in San Francisco, 600 16th Street Mission Bay/Genentech Hall, Room N212, San Francisco, CA, 94143, USA

    Wei Wu

Authors
  1. Wei Cao
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Wenfang Cheng
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Wei Wu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Wei Cao .

Editor information

Editors and Affiliations

  1. Department of Medicine, Helen Diller Family Comprehensive Cancer Center, University of California in San Francisco, San Francisco, California, USA

    Wei Wu

Rights and permissions

Reprints and permissions

Copyright information

© 2018 Springer Science+Business Media LLC

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Cao, W., Cheng, W., Wu, W. (2018). MicroRNAs Reprogram Tumor Immune Response. In: Wu, W. (eds) MicroRNA and Cancer. Methods in Molecular Biology, vol 1699. Humana Press, New York, NY. https://doi.org/10.1007/978-1-4939-7435-1_4

Download citation

  • DOI: https://doi.org/10.1007/978-1-4939-7435-1_4

  • Published:

  • Publisher Name: Humana Press, New York, NY

  • Print ISBN: 978-1-4939-7433-7

  • Online ISBN: 978-1-4939-7435-1

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation