Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1994 Jun;69(6):1078–1082. doi: 10.1038/bjc.1994.211

Limited heterogeneity in the T-cell receptor V-gene usage in lymphocytes infiltrating human colorectal tumours.

B Ostenstad 1, M Sioud 1, T Lea 1, E Schlichting 1, M Harboe 1
PMCID: PMC1969442  PMID: 8198973

Abstract

The presence of T lymphocytes in solid tumours may reflect an ongoing immune response against the transformed cells. We have used polymerase chain reaction (PCR) technology to investigate the T-cell receptor variable-region gene (V-gene) usage in freshly isolated tumour-infiltrating lymphocytes (TILs) to look for a possible oligoclonality of T cells in the tumour area. We used 19 different V beta-family-specific primers. Peripheral blood lymphocytes and lamina propria lymphocytes from the same patients were also tested by PCR. Our results demonstrate a limited heterogeneity in the V-gene usage of TILs from seven patients with colorectal cancers, suggesting a local antigen-driven immune response at the tumour site.

Full text

PDF
1078

Images in this article

Selected References

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

  1. Belldegrun A., Kasid A., Uppenkamp M., Topalian S. L., Rosenberg S. A. Human tumor infiltrating lymphocytes. Analysis of lymphokine mRNA expression and relevance to cancer immunotherapy. J Immunol. 1989 Jun 15;142(12):4520–4526. [PubMed] [Google Scholar]
  2. Chen L., Ashe S., Brady W. A., Hellström I., Hellström K. E., Ledbetter J. A., McGowan P., Linsley P. S. Costimulation of antitumor immunity by the B7 counterreceptor for the T lymphocyte molecules CD28 and CTLA-4. Cell. 1992 Dec 24;71(7):1093–1102. doi: 10.1016/s0092-8674(05)80059-5. [DOI] [PubMed] [Google Scholar]
  3. Chomczynski P., Sacchi N. Single-step method of RNA isolation by acid guanidinium thiocyanate-phenol-chloroform extraction. Anal Biochem. 1987 Apr;162(1):156–159. doi: 10.1006/abio.1987.9999. [DOI] [PubMed] [Google Scholar]
  4. Davies T. F., Concepcion E. S., Ben-Nun A., Graves P. N., Tarjan G. T-cell receptor V gene use in autoimmune thyroid disease: direct assessment by thyroid aspiration. J Clin Endocrinol Metab. 1993 Mar;76(3):660–666. doi: 10.1210/jcem.76.3.8445022. [DOI] [PubMed] [Google Scholar]
  5. Fearon E. R., Pardoll D. M., Itaya T., Golumbek P., Levitsky H. I., Simons J. W., Karasuyama H., Vogelstein B., Frost P. Interleukin-2 production by tumor cells bypasses T helper function in the generation of an antitumor response. Cell. 1990 Feb 9;60(3):397–403. doi: 10.1016/0092-8674(90)90591-2. [DOI] [PubMed] [Google Scholar]
  6. Fearon E. R., Vogelstein B. A genetic model for colorectal tumorigenesis. Cell. 1990 Jun 1;61(5):759–767. doi: 10.1016/0092-8674(90)90186-i. [DOI] [PubMed] [Google Scholar]
  7. Ferradini L., Mackensen A., Genevée C., Bosq J., Duvillard P., Avril M. F., Hercend T. Analysis of T cell receptor variability in tumor-infiltrating lymphocytes from a human regressive melanoma. Evidence for in situ T cell clonal expansion. J Clin Invest. 1993 Mar;91(3):1183–1190. doi: 10.1172/JCI116278. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ferradini L., Roman-Roman S., Azocar J., Avril M. F., Viel S., Triebel F., Hercend T. Analysis of T-cell receptor alpha/beta variability in lymphocytes infiltrating a melanoma metastasis. Cancer Res. 1992 Sep 1;52(17):4649–4654. [PubMed] [Google Scholar]
  9. Gelber C., Eisenbach L., Feldman M., Goodenow R. S. T-cell subset analysis of Lewis lung carcinoma tumor rejection: heterogeneity of effectors and evidence for negative regulatory lymphocytes correlating with metastasis. Cancer Res. 1992 Dec 1;52(23):6507–6515. [PubMed] [Google Scholar]
  10. Golumbek P. T., Lazenby A. J., Levitsky H. I., Jaffee L. M., Karasuyama H., Baker M., Pardoll D. M. Treatment of established renal cancer by tumor cells engineered to secrete interleukin-4. Science. 1991 Nov 1;254(5032):713–716. doi: 10.1126/science.1948050. [DOI] [PubMed] [Google Scholar]
  11. Hom S. S., Rosenberg S. A., Topalian S. L. Specific immune recognition of autologous tumor by lymphocytes infiltrating colon carcinomas: analysis by cytokine secretion. Cancer Immunol Immunother. 1993;36(1):1–8. doi: 10.1007/BF01789124. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Hérin M., Lemoine C., Weynants P., Vessière F., Van Pel A., Knuth A., Devos R., Boon T. Production of stable cytolytic T-cell clones directed against autologous human melanoma. Int J Cancer. 1987 Mar 15;39(3):390–396. doi: 10.1002/ijc.2910390320. [DOI] [PubMed] [Google Scholar]
  13. Ibrahim S., Dawson D. V., Elmohsen M. A., Elsamannoudy F. A., Sanfilippo F. Differential expression of T-cell receptor-V region determinants on infiltrating T cells in rejecting and nonrejecting human kidney, liver, and heart allografts. Transplant Proc. 1993 Feb;25(1 Pt 1):80–83. [PubMed] [Google Scholar]
  14. Ioannides C. G., Fisk B., Pollack M. S., Frazier M. L., Taylor Wharton J., Freedman R. S. Cytotoxic T-cell clones isolated from ovarian tumour infiltrating lymphocytes recognize common determinants on non-ovarian tumour clones. Scand J Immunol. 1993 Apr;37(4):413–424. doi: 10.1111/j.1365-3083.1993.tb03312.x. [DOI] [PubMed] [Google Scholar]
  15. Itoh K., Platsoucas C. D., Balch C. M. Autologous tumor-specific cytotoxic T lymphocytes in the infiltrate of human metastatic melanomas. Activation by interleukin 2 and autologous tumor cells, and involvement of the T cell receptor. J Exp Med. 1988 Oct 1;168(4):1419–1441. doi: 10.1084/jem.168.4.1419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Jass J. R. Lymphocytic infiltration and survival in rectal cancer. J Clin Pathol. 1986 Jun;39(6):585–589. doi: 10.1136/jcp.39.6.585. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Karpati R. M., Banks S. M., Malissen B., Rosenberg S. A., Sheard M. A., Weber J. S., Hodes R. J. Phenotypic characterization of murine tumor-infiltrating T lymphocytes. J Immunol. 1991 Mar 15;146(6):2043–2051. [PubMed] [Google Scholar]
  18. Mak T. W. The T-cell antigen receptor enters its second decade. Scand J Immunol. 1993 Sep;38(3):209–211. doi: 10.1111/j.1365-3083.1993.tb01715.x. [DOI] [PubMed] [Google Scholar]
  19. Morita T., Salmeron M. A., Moser R. P., Ross M. I., Itoh K. Oligoclonal expansion of V beta 8+ cells in interleukin-2-activated T cells residing in subcutaneous metastatic melanoma. Clin Exp Metastasis. 1992 Jan;10(1):69–76. doi: 10.1007/BF00163578. [DOI] [PubMed] [Google Scholar]
  20. Nitta T., Bell R., Okumura K., Sato K., Steinman L. T-cell receptor V beta gene expression differs in tumor-infiltrating lymphocytes within primary and metastatic melanoma. Cancer Res. 1991 Oct 15;51(20):5565–5569. [PubMed] [Google Scholar]
  21. Ostenstad B., Lea T., Schlichting E., Harboe M. Human colorectal tumour infiltrating lymphocytes express activation markers and the CD45RO molecule, showing a primed population of lymphocytes in the tumour area. Gut. 1994 Mar;35(3):382–387. doi: 10.1136/gut.35.3.382. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Rosenberg S. A., Packard B. S., Aebersold P. M., Solomon D., Topalian S. L., Toy S. T., Simon P., Lotze M. T., Yang J. C., Seipp C. A. Use of tumor-infiltrating lymphocytes and interleukin-2 in the immunotherapy of patients with metastatic melanoma. A preliminary report. N Engl J Med. 1988 Dec 22;319(25):1676–1680. doi: 10.1056/NEJM198812223192527. [DOI] [PubMed] [Google Scholar]
  23. Sioud M., Kjeldsen-Kragh J., Quayle A. J., Wiker H. G., Sørskaar D., Natvig J. B., Førre O. Immune responses to 18.6 and 30-kDa mycobacterial antigens in rheumatoid patients, and V beta usage by specific synovial T-cell lines and fresh T cells. Scand J Immunol. 1991 Dec;34(6):803–812. doi: 10.1111/j.1365-3083.1991.tb01605.x. [DOI] [PubMed] [Google Scholar]
  24. Sioud M., Kjeldsen-Kragh J., Suleyman S., Vinje O., Natvig J. B., Førre O. Limited heterogeneity of T cell receptor variable region gene usage in juvenile rheumatoid arthritis synovial T cells. Eur J Immunol. 1992 Sep;22(9):2413–2418. doi: 10.1002/eji.1830220934. [DOI] [PubMed] [Google Scholar]
  25. Svennevig J. L., Lunde O. C., Holter J., Bjørgsvik D. Lymphoid infiltration and prognosis in colorectal carcinoma. Br J Cancer. 1984 Mar;49(3):375–377. doi: 10.1038/bjc.1984.60. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Topalian S. L., Muul L. M., Solomon D., Rosenberg S. A. Expansion of human tumor infiltrating lymphocytes for use in immunotherapy trials. J Immunol Methods. 1987 Aug 24;102(1):127–141. doi: 10.1016/s0022-1759(87)80018-2. [DOI] [PubMed] [Google Scholar]
  27. Urban J. L., Kripke M. L., Schreiber H. Stepwise immunologic selection of antigenic variants during tumor growth. J Immunol. 1986 Nov 1;137(9):3036–3041. [PubMed] [Google Scholar]
  28. Weidmann E., Whiteside T. L., Giorda R., Herberman R. B., Trucco M. The T-cell receptor V beta gene usage in tumor-infiltrating lymphocytes and blood of patients with hepatocellular carcinoma. Cancer Res. 1992 Nov 1;52(21):5913–5920. [PubMed] [Google Scholar]
  29. Wong F. S., Hibberd M. L., Wen L., Millward B. A., Demaine A. G. The human T cell receptor V beta repertoire of normal peripheral blood lymphocytes before and after mitogen stimulation. Clin Exp Immunol. 1993 May;92(2):361–366. doi: 10.1111/j.1365-2249.1993.tb03405.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yasumura S., Hirabayashi H., Schwartz D. R., Toso J. F., Johnson J. T., Herberman R. B., Whiteside T. L. Human cytotoxic T-cell lines with restricted specificity for squamous cell carcinoma of the head and neck. Cancer Res. 1993 Mar 15;53(6):1461–1468. [PubMed] [Google Scholar]
  31. van der Bruggen P., Traversari C., Chomez P., Lurquin C., De Plaen E., Van den Eynde B., Knuth A., Boon T. A gene encoding an antigen recognized by cytolytic T lymphocytes on a human melanoma. Science. 1991 Dec 13;254(5038):1643–1647. doi: 10.1126/science.1840703. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES