Skip to main content
NCBI home page
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1994 Feb;95(2):232–236. doi: 10.1111/j.1365-2249.1994.tb06516.x

Follow up of soluble IL-2 receptor level in metastatic malignant melanoma patients treated by chemoimmunotherapy.

C Soubrane 1, R Mouawad 1, M Ichen 1, J Suissa 1, C Borel 1, E Vuillemin 1, A Benhammouda 1, J P Bizzari 1, M Weil 1, D Khayat 1
PMCID: PMC1534932  PMID: 8306497

Abstract

Immunological parameters following chemoimmunotherapy combination were studied in 31 patients with metastatic malignant melanoma. They received Cisplatin (100 mg/m2) on day 1 and 28, recombinant IL-2 (rIL-2; Eurocetus) in continuous infusion from day 3 to 6, 17 to 21, 31 to 34 and 45 to 49. Interferon-alpha (IFN-alpha; Roche) was given subcutaneously three times weekly. No significant change in CD4/CD8 ratio at onset or during treatment was observed between responder (n = 19) and non-responder (n = 12) patients. Regarding the IL-2 receptor (IL-2R) study, the percentage of cells expressing Tac (p55) receptor did not change either for healthy volunteers (n = 20) and patients before any therapy, or between responder and non-responder patients. Concerning serum soluble IL-2R shedding before therapy, we observed a significant increase (P = 0.001) in patients (79 +/- 40 pM) compared with healthy donors (30 +/- 15 pM), but no significant variation was seen between responder and non-responder patients. In contrast, during the treatment, the soluble IL-2R level increased in both groups but, interestingly, a significant difference was found between responder and non-responder patients from day 7 (P < 0.05) to day 21 (P < or = 0.01), suggesting that the cells from non-responder may be slower in becoming stimulated. This finding is the most striking point of our study and suggests that sIL-2R might be an early predictive factor of the clinical response as obtained by logistic regression (P = 0.0063). Therefore patients with a serum soluble IL-2R level greater than 250 pM at day 21 have a 12-fold more chance of undergoing a clinical response.

Full text

PDF
232

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Blay J. Y., Favrot M. C., Negrier S., Combaret V., Chouaib S., Mercatello A., Kaemmerlen P., Franks C. R., Philip T. Correlation between clinical response to interleukin 2 therapy and sustained production of tumor necrosis factor. Cancer Res. 1990 Apr 15;50(8):2371–2374. [PubMed] [Google Scholar]
  2. Carey R. W., Anderson J. R., Green M., Ellison R. R., Nathanson L., Kennedy B. J. Treatment of metastatic malignant melanoma with vinblastine, dacarbazine, and cisplatin: a report from the Cancer and Leukemia Group B. Cancer Treat Rep. 1986 Mar;70(3):329–331. [PubMed] [Google Scholar]
  3. Chilosi M., Semenzato G., Cetto G., Ambrosetti A., Fiore-Donati L., Perona G., Berton G., Lestani M., Scarpa A., Agostini C. Soluble interleukin-2 receptors in the sera of patients with hairy cell leukemia: relationship with the effect of recombinant alpha-interferon therapy on clinical parameters and natural killer in vitro activity. Blood. 1987 Nov;70(5):1530–1535. [PubMed] [Google Scholar]
  4. Ellis T. M., Fisher R. I. Functional heterogeneity of Leu 19"bright"+ and Leu 19"dim"+ lymphokine-activated killer cells. J Immunol. 1989 Apr 15;142(8):2949–2954. [PubMed] [Google Scholar]
  5. Favrot M. C., Combaret V., Negrier S., Philip I., Thiesse P., Freydel C., Bijmann J. T., Franks C. R., Mercatello A., Philip T. Functional and immunophenotypic modifications induced by interleukin-2 did not predict response to therapy in patients with renal cell carcinoma. J Biol Response Mod. 1990 Apr;9(2):167–177. [PubMed] [Google Scholar]
  6. Gottlieb D. J., Prentice H. G., Heslop H. E., Bello C., Brenner M. K. IL-2 infusion abrogates humoral immune responses in humans. Clin Exp Immunol. 1992 Mar;87(3):493–498. doi: 10.1111/j.1365-2249.1992.tb03025.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Gundersen S. Dacarbazine, vindesine, and cisplatin combination chemotherapy in advanced malignant melanoma: a phase II study. Cancer Treat Rep. 1987 Nov;71(11):997–999. [PubMed] [Google Scholar]
  8. Hayat K., Rodgers S., Bruce L., Rees R. C., Chapman K., Reeder S., Dorreen M. S., Sheridan E., Sreenivasan T., Hancock B. W. Malignant melanoma and renal cell carcinoma: immunological and haematological effects of recombinant human interleukin-2. Eur J Cancer. 1991;27(8):1009–1014. doi: 10.1016/0277-5379(91)90270-n. [DOI] [PubMed] [Google Scholar]
  9. Itoh K., Shiiba K., Shimizu Y., Suzuki R., Kumagai K. Generation of activated killer (AK) cells by recombinant interleukin 2 (rIL 2) in collaboration with interferon-gamma (IFN-gamma). J Immunol. 1985 May;134(5):3124–3129. [PubMed] [Google Scholar]
  10. Khayat D., Borel C., Tourani J. M., Benhammouda A., Antoine E., Rixe O., Vuillemin E., Bazex P. A., Thill L., Franks R. Sequential chemoimmunotherapy with cisplatin, interleukin-2, and interferon alfa-2a for metastatic melanoma. J Clin Oncol. 1993 Nov;11(11):2173–2180. doi: 10.1200/JCO.1993.11.11.2173. [DOI] [PubMed] [Google Scholar]
  11. Lanier L. L., Benike C. J., Phillips J. H., Engleman E. G. Recombinant interleukin 2 enhanced natural killer cell-mediated cytotoxicity in human lymphocyte subpopulations expressing the Leu 7 and Leu 11 antigens. J Immunol. 1985 Feb;134(2):794–801. [PubMed] [Google Scholar]
  12. Lanier L. L., Le A. M., Civin C. I., Loken M. R., Phillips J. H. The relationship of CD16 (Leu-11) and Leu-19 (NKH-1) antigen expression on human peripheral blood NK cells and cytotoxic T lymphocytes. J Immunol. 1986 Jun 15;136(12):4480–4486. [PubMed] [Google Scholar]
  13. Legha S. S. Current therapy for malignant melanoma. Semin Oncol. 1989 Feb;16(1 Suppl 1):34–44. [PubMed] [Google Scholar]
  14. Lissoni P., Barni S., Ardizzoia A., Crispino S., Paolorossi F., Archili C., Vaghi M., Tancini G. Second line therapy with low-dose subcutaneous interleukin-2 alone in advanced renal cancer patients resistant to interferon-alpha. Eur J Cancer. 1992;28(1):92–96. doi: 10.1016/0959-8049(92)90393-g. [DOI] [PubMed] [Google Scholar]
  15. McIntyre C. A., Chapman K., Reeder S., Dorreen M. S., Bruce L., Rodgers S., Hayat K., Schreenivasan T., Sheridan E., Hancock B. W. Treatment of malignant melanoma and renal cell carcinoma with recombinant human interleukin-2: analysis of cytokine levels in sera and culture supernatants. Eur J Cancer. 1992;28(1):58–63. doi: 10.1016/0959-8049(92)90385-f. [DOI] [PubMed] [Google Scholar]
  16. Mitchell M. S., Kempf R. A., Harel W., Shau H., Boswell W. D., Lind S., Bradley E. C. Effectiveness and tolerability of low-dose cyclophosphamide and low-dose intravenous interleukin-2 in disseminated melanoma [corrected]. J Clin Oncol. 1988 Mar;6(3):409–424. doi: 10.1200/JCO.1988.6.3.409. [DOI] [PubMed] [Google Scholar]
  17. Nagler A., Lanier L. L., Cwirla S., Phillips J. H. Comparative studies of human FcRIII-positive and negative natural killer cells. J Immunol. 1989 Nov 15;143(10):3183–3191. [PubMed] [Google Scholar]
  18. Richards J. M., Mick R., Latta J. M., Daly K., Ratain M. J., Vardiman J. W., Golomb H. M. Serum soluble interleukin-2 receptor is associated with clinical and pathologic disease status in hairy cell leukemia. Blood. 1990 Nov 15;76(10):1941–1945. [PubMed] [Google Scholar]
  19. Rosenberg S. A., Lotze M. T., Muul L. M., Chang A. E., Avis F. P., Leitman S., Linehan W. M., Robertson C. N., Lee R. E., Rubin J. T. A progress report on the treatment of 157 patients with advanced cancer using lymphokine-activated killer cells and interleukin-2 or high-dose interleukin-2 alone. N Engl J Med. 1987 Apr 9;316(15):889–897. doi: 10.1056/NEJM198704093161501. [DOI] [PubMed] [Google Scholar]
  20. Rosenberg S. A., Lotze M. T., Yang J. C., Linehan W. M., Seipp C., Calabro S., Karp S. E., Sherry R. M., Steinberg S., White D. E. Combination therapy with interleukin-2 and alpha-interferon for the treatment of patients with advanced cancer. J Clin Oncol. 1989 Dec;7(12):1863–1874. doi: 10.1200/JCO.1989.7.12.1863. [DOI] [PubMed] [Google Scholar]
  21. Rosenberg S. A., Mulé J. J., Spiess P. J., Reichert C. M., Schwarz S. L. Regression of established pulmonary metastases and subcutaneous tumor mediated by the systemic administration of high-dose recombinant interleukin 2. J Exp Med. 1985 May 1;161(5):1169–1188. doi: 10.1084/jem.161.5.1169. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rubin L. A., Jay G., Nelson D. L. The released interleukin 2 receptor binds interleukin 2 efficiently. J Immunol. 1986 Dec 15;137(12):3841–3844. [PubMed] [Google Scholar]
  23. Urba W. J., Steis R. G., Longo D. L., Kopp W. C., Maluish A. E., Marcon L., Nelson D. L., Stevenson H. C., Clark J. W. Immunomodulatory properties and toxicity of interleukin 2 in patients with cancer. Cancer Res. 1990 Jan 1;50(1):185–192. [PubMed] [Google Scholar]
  24. Voss S. D., Hank J. A., Nobis C. A., Fisch P., Sosman J. A., Sondel P. M. Serum levels of the low-affinity interleukin-2 receptor molecule (TAC) during IL-2 therapy reflect systemic lymphoid mass activation. Cancer Immunol Immunother. 1989;29(4):261–269. doi: 10.1007/BF00199214. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Voss S. D., Sondel P. M., Robb R. J. Characterization of the interleukin 2 receptors (IL-2R) expressed on human natural killer cells activated in vivo by IL-2: association of the p64 IL-2R gamma chain with the IL-2R beta chain in functional intermediate-affinity IL-2R. J Exp Med. 1992 Aug 1;176(2):531–541. doi: 10.1084/jem.176.2.531. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Weil-Hillman G., Fisch P., Prieve A. F., Sosman J. A., Hank J. A., Sondel P. M. Lymphokine-activated killer activity induced by in vivo interleukin 2 therapy: predominant role for lymphocytes with increased expression of CD2 and leu19 antigens but negative expression of CD16 antigens. Cancer Res. 1989 Jul 1;49(13):3680–3688. [PubMed] [Google Scholar]
  27. Weiner L. M., Padavic-Shaller K., Kitson J., Watts P., Krigel R. L., Litwin S. Phase I evaluation of combination therapy with interleukin 2 and gamma-interferon. Cancer Res. 1991 Aug 1;51(15):3910–3918. [PubMed] [Google Scholar]
  28. Weiner L. M., Steplewski Z., Koprowski H., Litwin S., Comis R. L. Divergent dose-related effects of gamma-interferon therapy on in vitro antibody-dependent cellular and nonspecific cytotoxicity by human peripheral blood monocytes. Cancer Res. 1988 Feb 15;48(4):1042–1046. [PubMed] [Google Scholar]

Articles from Clinical and Experimental Immunology are provided here courtesy of British Society for Immunology

RESOURCES