Springer Nature is making SARS-CoV-2 and COVID-19 research free. View research | View latest news | Sign up for updates

Indomethacin-induced augmentation of lymphoproliferative responses in patients with head and neck cancer

  • 10 Accesses

  • 16 Citations

Summary

Augmentation of the phytohemagglutinin (PHA)-induced lymphoproliferation of peripheral blood mononuclear cells by indomethacin, a drug which blocks prostaglandin (PG) synthesis, was assessed in 37 patients with squamous cell carcinoma of the head and neck. Indomethacin enhanced the uptake of 3H-thymidine in stimulated cultures both from patients and normal individuals. However, because lymphoid cells from cancer patients were less reactive than those from normal controls, the proportionate increase in PHA-stimulated 3H-thymidine incorporation caused by indomethacin was greater in this population than in the normal population. The degree of enhancement induced by indomethacin did not correlate with the percent of esterase-positive mononuclear cells in the preparations. The amounts of PGE synthesized at 48 h by patients' or normal cells were similar. Cell populations that exhibited elevated levels of augmentation in the presence of indomethacin were approximately 3 times as sensitive to inhibition by 3 nM PGE2. The degree of augmentation detected in the presence of Ro-20-5720, which also prevents PG synthesis, was related to that produced by indomethacin. These results suggested that: (1) the enhancing effect of indomethacin on lymphoproliferation in vitro was related to its inhibition of PG synthesis; and (2) the sensitivity of lymphoid cells to inhibition by PGE2 was slightly, but significantly, increased in individuals with elevated augmentation values.

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

References

  1. 1.

    Al-Saleem T, Ali ZS, Qassab M (1980) Skin cancers in xeroderma pigmentosum: response to indomethacin and steroids. Lancet II:264

  2. 2.

    Bennett A (1979) Prostaglandins and cancer. In: Karim SMM (ed) Practical applications of prostaglandins and their synthesis inhibitors. MTP Press, Lancaster, p 149

  3. 3.

    Berlinger, NT, Hilal EY, Oettgen, HF, Good RA (1978) Deficient cell-mediated immunity in head and neck cancer patients secondary to autologous suppressive immune cells. Laryngoscope 88:470

  4. 4.

    Braun DP, Harris JE (1984) Effect of combination chemotherapy on PGE-mediated immunoregulation in the peripheral blood mononuclear cells of solid tumor cancer patients. J Biol Response Mod 3:391

  5. 5.

    Braun DP, Harris JE (1984) Abnormal indomethacin-sensitive suppression in peripheral blood mononuclear cells of cancer patients restricts augmentation by interleukin-2. J Biol Response Mod 3:533

  6. 6.

    Braun DP, Cobleigh MA, Harris JE (1980) Multiple concurrent immunoregulatory defects in cancer patients with depressed PHA-induced lymphocyte DNA synthesis. Clin Immunol Immunopathol 17:89

  7. 7.

    Braun DP, Penn RD, Flannery AM, Harris JE (1982) Immunoregulatory cell function in peripheral blood leukocytes of patients with intracranial gliomas. Neurosurgery 10:203

  8. 8.

    Braun DP, Nisius S, Hollinshead A, Harris JE (1983) Serial immune testing in surgically resected lung cancer patients. Cancer Immunol Immunother 15:114

  9. 9.

    Browder JP, Chretien PB (1977) Immune reactivity in head and neck squamous carcinoma and relevance to the design of immunotherapy trials. Sem Oncol 4:431

  10. 10.

    Carter CA, Milholland RJ, Shea W, Ip MM (1983) Effect of the prostaglandin synthetase inhibitor indomethacin on 7, 12-dimethylbenz(a)anthracene-induced mammary tumorigenesis in rats fed different levels of fat. Cancer Res 43:3559

  11. 11.

    Chouaib S, Chatenoud L, Klatzmann D, Fradelizi D (1984) The mechanisms of inhibition of human IL2 production. II. PGE2 induction of suppressor T lymphocytes. J Immunol 132:1851

  12. 12.

    Dawson DE, Everts EC, Vetto RM, Burger DR (1985) Assessment of immunocompetent cells in patients with head and neck squamous cell carcinoma. Ann Otol Rhinol Laryngol 94:342

  13. 13.

    DeGowin RL, Gibson DP (1981) Prostaglandin-mediated enhancement of erythroid colonies by marrow stromal cells (MSC). Exp Hematol 9:274

  14. 14.

    DeShazo RD (1980) Indomethacin-responsive mononuclear cell dysfunction in Hodgkin's disease. Clin Immunol Immunopathol 17:66

  15. 15.

    Flower RJ (1974) Drugs which inhibit prostaglandin biosynthesis. Pharmacol Rev 26:33

  16. 16.

    Fulton AM (1984) In vivo effects of indomethacin on the growth of murine mammary tumors. Cancer Res 44:2416

  17. 17.

    Goldyne ME, Stobo JD (1980) Prostaglandin E2 as a modulator of macrophage-T lymphocyte interactions. J Invest Dermatol 74:297

  18. 18.

    Goodwin JS, Webb DR (1980) Regulation of the immune response by prostaglandin. Clin Immunol Immunopathol 15:106

  19. 19.

    Goodwin JS, Messner RP, Bankhurst AD, Peak GT, Saiki JH, Williams RC Jr (1977) Prostaglandin-producing suppressor cells in Hodgkin's disease. N Engl J Med 297:963

  20. 20.

    Goodwin JS, Bankhurst AD, Murphy SA, Selinger DS, Messner RP, Williams RC Jr (1978) Partial reversal of the cellular immune defect in common variable immunodeficiency with indomethacin. J Clin Lab Immunol 1:197

  21. 21.

    Goodwin JS, Selinger DS, Messner RP, Reed WP (1978) Effect of indomethacin in vivo on humoral and cellular immunity in humans. Infect Immun 19:430

  22. 22.

    Goodwin JS, Bromberg S, Staszak C, Kaszubowski PA, Messner RP, Neal JF (1981) Effect of physical stress on sensitivity of lymphocytes to inhibition by prostaglandin E. J Immunol 127:518

  23. 23.

    Hayashi Y, Nishida T, Yoshida H, Yanagawa T, Yura Y, Furumoto N, Sato M (1984) Peripheral T γ lymphocyte population in head and neck cancer. Cancer Immunol Immunother 17:160

  24. 24.

    Hirsch B, Johnson JT, Rabin BS, Thearle PB (1983) Immunostimulation of patients with head and neck cancer. Arch Otolaryngol 109:298

  25. 25.

    Kantor HS, Hampton M (1978) Indomethacin in submicromolar concentrations inhibits cyclic AMP-dependent protein kinase. Nature 276:841

  26. 26.

    Kollmorgen GM, King MM, Kosanke SD, Do C (1983) Influence of dietary fat and indomethacin on the growth of transplantable mammary tumors in rats. Cancer Res 43:4714

  27. 27.

    Koski IR, Poplack DG, Blaese RM (1976) A nonspecific esterase stain for the identification of monocytes and macrophages. In: Bloom BR, David JR (eds) In vitro methods in cell-mediated and tumor immunity. Academic Press, New York, p 359

  28. 28.

    Lewis GP (1983) Immunoregulatory activity of metabolites of arachidonic acid and their role in inflammation. Br Med Bull 39:243

  29. 29.

    Lynch NR, Castes M, Astoin M, Salomon JC (1978) Mechanism of inhibition of tumor growth by aspirin and indomethacin. Br J Cancer 38:503

  30. 30.

    Maca RD, Panje WR (1982) Indomethacin sensitive suppressor cell activity in head and neck cancer patients pre- and post irradiation therapy. Cancer 50:483

  31. 31.

    Mavligit GM, Raphael LS, Calvo DB III, Wong WL (1980) Indomethacin-induced, monocyte-dependent restoration of local graft-versus-host reaction among cells from cancer patients. J Natl Cancer Inst 65:317

  32. 32.

    Murray JL, Springle C, Ishmael DR, Lee ET, Longley R, Kollmorgen GM, Nordquist RL (1981) Adherent indomethacin-sensitive suppressor cells in malignant melanoma. Correlation with clinical status. Cancer Immunol Immunother 11:165

  33. 33.

    Narisawa T, Sato M, Tani M, Kudo T, Takahashi T, Goto A (1981) Inhibition of development of methylnitrosourea-induced rat colon tumors by indomethacin treatment. Cancer Res 41:1954

  34. 34.

    Panje WR (1981) Regression of head and neck carcinoma with a prostaglandin-synthesis inhibitor. Arch Orolaryngol 107:658

  35. 35.

    Panje WR (1983) Prostaglandin synthesis inhibitor in the treatment of head and neck cancer. In: Rhys Evans PH, Robin PE, Fielding JWL (eds) Head and neck cancer. Castle House Publications Ltd, Tunbridge Wells, p 105

  36. 36.

    Pelus LM, Strausser HR (1976) Indomethacin enhancement of spleen-cell responsiveness to mitogen stimulation in tumorous mice. Int J Cancer 18:653

  37. 37.

    Plescia OJ (1982) Does prostaglandin synthesis effect in vivo tumour growth by altering tumor/host balance? In: Powles TJ, Bockman RS, Honn KV, et al (eds) Prostaglandins and cancer: first international conference. Alan R Liss, Inc, New York, p 619

  38. 38.

    Plescia OJ, Smith AH, Grinwich K (1975) Subversion of immune system by tumor cells and role of prostaglandins. Proc Natl Acad Sci USA 72:1848

  39. 39.

    Pollard M, Luckert PH (1980) Indomethacin treatment of rats with dimethylhydrazine-induced intestinal tumors. Cancer Treat Rep 64:1323

  40. 40.

    Pollard M, Luckert PH (1981) Effect of indomethacin on intestinal tumors induced in rats by the acetate derivative of dimethylnitrosamine. Science 214:558

  41. 41.

    Powles TJ, personal communication to Bennett A, ref 2, p 170

  42. 42.

    Stockman GD, Mumford DM (1974) The effect of prostaglandins on the in vitro blastogenic response of human peripheral blood lymphocytes. Exp Hematol 2:65

  43. 43.

    Stoll BA (1973) Indomethacin in breast cancer. Lancet II:384

  44. 44.

    Strausser HR, Humes JL (1975) Prostaglandin synthesis inhibition: effect on bone changes and sarcoma tumor induction in BALB/c mice. Int J Cancer 15:724

  45. 45.

    Tilden AB, Balch CM (1981) Indomethacin enhancement of immunocompetence in melanoma patients. Surgery 90:77

  46. 46.

    Tilden AB, Dougherty PA, Balch CM (1982) Differential effects of indomethacin and PGE2 on the depressed responses of cancer patients. In: Powles TJ, Bockman RS, Honn KV, et al. (eds) Prostaglandins and cancer: first international conference. Alan R Liss, Inc, New York, p 651

  47. 47.

    Trevisani A, Ferreti E, Capuzzo A, Tomasi V (1980) Elevated levels of prostaglandin E2 in Yoshida hepatoma and the inhibition of tumor growth by non-steroidal anti-inflammatory drugs. Br J Cancer 41:341

  48. 48.

    Vosixa G, Thies J (1979) Effect of indomethacin on blastogenesis of lymphocytes from cancer patients: differentiation of patient types. Clin Immunol Immunopathol 13:30

  49. 49.

    Waddell WR, Gerner RE (1980) Indomethacin and ascorbate inhibit desmoid tumors. J Surg Oncol 15:85

  50. 50.

    Young MR, Knies S (1984) Prostaglandin E production by Lewis lung carcinoma: mechanism for tumor establishment in vivo. J Natl Cancer Inst 72:919

  51. 51.

    Zighelboim J, Dorey F, Parker NH, Calcaterra T, Ward P, Fahey JL (1979) Immunologic evaluation of patients with advanced head and neck carcinoma receiving weekly chemoimmunotherapy. Cancer 44:117

Download references

Author information

Correspondence to Kenneth J. McCormick.

Additional information

A portion of this study was completed at the Division of Head and Neck Surgical Oncology, Department of Otolaryngology-Head and Neck Surgery, The University of Iowa Hospitals and Clinics, Iowa City, IA 52242, USA

Rights and permissions

Reprints and Permissions

About this article

Cite this article

McCormick, K.J., Panje, W.R. Indomethacin-induced augmentation of lymphoproliferative responses in patients with head and neck cancer. Cancer Immunol Immunother 21, 226–232 (1986). https://doi.org/10.1007/BF00199366

Download citation

Keywords

  • Carcinoma
  • Squamous Cell Carcinoma
  • Squamous Cell
  • Prostaglandin
  • Mononuclear Cell