Skip to main content
Clinical and Experimental Immunology logoLink to Clinical and Experimental Immunology
. 1993 Sep;93(3):442–447. doi: 10.1111/j.1365-2249.1993.tb08198.x

Functional analysis of TCR gamma delta+ T cells in tumour-infiltrating lymphocytes (TIL) of human pancreatic cancer.

J Kitayama 1, Y Atomi 1, H Nagawa 1, A Kuroda 1, T Mutoh 1, M Minami 1, T Juji 1
PMCID: PMC1554920  PMID: 8370173

Abstract

In six patients with advanced pancreatic carcinoma, TIL and tumour-draining lymphocytes (TDL) were isolated from primary pancreatic tumour and regional lymph nodes. In comparison with TDL and peripheral blood lymphocytes (PBL), TIL contained a comparatively higher percentage of TCR gamma delta+ cells, although they were still a small fraction. By 2 weeks culture with rIL-2 and immobilized OKT-3 antibody, the TCR gamma delta+ cells in TIL were preferentially expanded at the early culture periods, although it was temporary. In four cases, the TCR gamma delta+ and CD8+ TCR alpha beta+ TIL were separated by negative sorting using flowcytometry. All the TCR gamma delta+ TIL were CD4-, CD8- (double negative), and one of the TIL lines was mostly composed of delta TCS1+ cells, while the others were delta TCS1-. In comparison with CD8+ TCR alpha beta+ TIL, all the TCR gamma delta+ TIL exhibited much stronger lytic activity against freshly isolated autologous pancreatic cancer cells. However, all the gamma delta+ TIL also exhibited a strong non-MHC-restricted cytotoxicity, and there was no correlation between the lytic pattern and the percentage of delta TCS1+ cells. These data suggest that the TCR gamma delta+ T cells can proliferate vigorously in a certain condition, and if successfully expanded in vitro they might be helpful material for effective adoptive immunotherapy.

Full text

PDF
442

Selected References

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

  1. Balch C. M., Riley L. B., Bae Y. J., Salmeron M. A., Platsoucas C. D., von Eschenbach A., Itoh K. Patterns of human tumor-infiltrating lymphocytes in 120 human cancers. Arch Surg. 1990 Feb;125(2):200–205. doi: 10.1001/archsurg.1990.01410140078012. [DOI] [PubMed] [Google Scholar]
  2. Brenner M. B., McLean J., Dialynas D. P., Strominger J. L., Smith J. A., Owen F. L., Seidman J. G., Ip S., Rosen F., Krangel M. S. Identification of a putative second T-cell receptor. Nature. 1986 Jul 10;322(6075):145–149. doi: 10.1038/322145a0. [DOI] [PubMed] [Google Scholar]
  3. Bruning J. W., Kardol M. J., Arentzen R. Carboxyfluorescein fluorochromasia assays. I. Non-radioactively labeled cell mediated lympholysis. J Immunol Methods. 1980;33(1):33–44. doi: 10.1016/0022-1759(80)90080-0. [DOI] [PubMed] [Google Scholar]
  4. Bucy R. P., Chen C. L., Cooper M. D. Tissue localization and CD8 accessory molecule expression of T gamma delta cells in humans. J Immunol. 1989 May 1;142(9):3045–3049. [PubMed] [Google Scholar]
  5. Ferrini S., Bottino C., Biassoni R., Poggi A., Sekaly R. P., Moretta L., Moretta A. Characterization of CD3+, CD4-, CD8- clones expressing the putative T cell receptor gamma gene product. Analysis of the activation pathways leading to interleukin 2 production and triggering of the lytic machinery. J Exp Med. 1987 Jul 1;166(1):277–282. doi: 10.1084/jem.166.1.277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Goodman T., Lefrançois L. Expression of the gamma-delta T-cell receptor on intestinal CD8+ intraepithelial lymphocytes. Nature. 1988 Jun 30;333(6176):855–858. doi: 10.1038/333855a0. [DOI] [PubMed] [Google Scholar]
  7. Groh V., Porcelli S., Fabbi M., Lanier L. L., Picker L. J., Anderson T., Warnke R. A., Bhan A. K., Strominger J. L., Brenner M. B. Human lymphocytes bearing T cell receptor gamma/delta are phenotypically diverse and evenly distributed throughout the lymphoid system. J Exp Med. 1989 Apr 1;169(4):1277–1294. doi: 10.1084/jem.169.4.1277. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Haregewoin A., Soman G., Hom R. C., Finberg R. W. Human gamma delta+ T cells respond to mycobacterial heat-shock protein. Nature. 1989 Jul 27;340(6231):309–312. doi: 10.1038/340309a0. [DOI] [PubMed] [Google Scholar]
  9. Holoshitz J., Koning F., Coligan J. E., De Bruyn J., Strober S. Isolation of CD4- CD8- mycobacteria-reactive T lymphocyte clones from rheumatoid arthritis synovial fluid. Nature. 1989 May 18;339(6221):226–229. doi: 10.1038/339226a0. [DOI] [PubMed] [Google Scholar]
  10. 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]
  11. Janeway C. A., Jr Frontiers of the immune system. Nature. 1988 Jun 30;333(6176):804–806. doi: 10.1038/333804a0. [DOI] [PubMed] [Google Scholar]
  12. Janssen O., Wesselborg S., Heckl-Ostreicher B., Pechhold K., Bender A., Schondelmaier S., Moldenhauer G., Kabelitz D. T cell receptor/CD3-signaling induces death by apoptosis in human T cell receptor gamma delta + T cells. J Immunol. 1991 Jan 1;146(1):35–39. [PubMed] [Google Scholar]
  13. Koide J., Rivas A., Engleman E. G. Natural killer (NK)-like cytotoxic activity of allospecific T cell receptor-gamma,delta+ T cell clones. Distinct receptor-ligand interactions mediate NK-like and allospecific cytotoxicity. J Immunol. 1989 Jun 15;142(12):4161–4168. [PubMed] [Google Scholar]
  14. Kradin R. L., Kurnick J. T., Lazarus D. S., Preffer F. I., Dubinett S. M., Pinto C. E., Gifford J., Davidson E., Grove B., Callahan R. J. Tumour-infiltrating lymphocytes and interleukin-2 in treatment of advanced cancer. Lancet. 1989 Mar 18;1(8638):577–580. doi: 10.1016/s0140-6736(89)91609-7. [DOI] [PubMed] [Google Scholar]
  15. Miescher S., Schreyer M., Barras C., Capasso P., von Fliedner V. Sparse distribution of gamma/delta T lymphocytes around human epithelial tumors predominantly infiltrated by primed/memory T cells. Cancer Immunol Immunother. 1990;32(2):81–87. doi: 10.1007/BF01754203. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Moretta L., Ciccone E., Ferrini S., Pelicci P. G., Mingari M. C., Zeromski J., Bottino C., Grossi C., Moretta A. Molecular and cellular analysis of human T lymphocytes expressing gamma delta T-cell receptor. Immunol Rev. 1991 Apr;120:117–135. doi: 10.1111/j.1600-065x.1991.tb00590.x. [DOI] [PubMed] [Google Scholar]
  17. Moretta L., Pende D., Bottino C., Migone N., Ciccone E., Ferrini S., Mingari M. C., Moretta A. Human CD3+4-8-WT31- T lymphocyte populations expressing the putative T cell receptor gamma-gene product. A limiting dilution and clonal analysis. Eur J Immunol. 1987 Sep;17(9):1229–1234. doi: 10.1002/eji.1830170903. [DOI] [PubMed] [Google Scholar]
  18. Muul L. M., Spiess P. J., Director E. P., Rosenberg S. A. Identification of specific cytolytic immune responses against autologous tumor in humans bearing malignant melanoma. J Immunol. 1987 Feb 1;138(3):989–995. [PubMed] [Google Scholar]
  19. Nanno M., Seki H., Mathioudakis G., Suzuki R., Itoh K., Ioannides C. G., Suzuki S., Chen P. F., Platsoucas C. D. Gamma/delta T cell antigen receptors expressed on tumor-infiltrating lymphocytes from patients with solid tumors. Eur J Immunol. 1992 Mar;22(3):679–687. doi: 10.1002/eji.1830220310. [DOI] [PubMed] [Google Scholar]
  20. Rosenberg S. A., Lotze M. T., Yang J. C., Aebersold P. M., Linehan W. M., Seipp C. A., White D. E. Experience with the use of high-dose interleukin-2 in the treatment of 652 cancer patients. Ann Surg. 1989 Oct;210(4):474–485. doi: 10.1097/00000658-198910000-00008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Rosenberg S. A., Spiess P., Lafreniere R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science. 1986 Sep 19;233(4770):1318–1321. doi: 10.1126/science.3489291. [DOI] [PubMed] [Google Scholar]
  22. Schoof D. D., Selleck C. M., Massaro A. F., Jung S. E., Eberlein T. J. Activation of human tumor-infiltrating lymphocytes by monoclonal antibodies directed to the CD3 complex. Cancer Res. 1990 Feb 15;50(4):1138–1143. [PubMed] [Google Scholar]
  23. Seki S., Abo T., Masuda T., Ohteki T., Kanno A., Takeda K., Rikiishi H., Nagura H., Kumagai K. Identification of activated T cell receptor gamma delta lymphocytes in the liver of tumor-bearing hosts. J Clin Invest. 1990 Aug;86(2):409–415. doi: 10.1172/JCI114726. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Takagi S., Chen K., Schwarz R., Iwatsuki S., Herberman R. B., Whiteside T. L. Functional and phenotypic analysis of tumor-infiltrating lymphocytes isolated from human primary and metastatic liver tumors and cultured in recombinant interleukin-2. Cancer. 1989 Jan 1;63(1):102–111. doi: 10.1002/1097-0142(19890101)63:1<102::aid-cncr2820630117>3.0.co;2-t. [DOI] [PubMed] [Google Scholar]
  25. Triebel F., Hercend T. Subpopulations of human peripheral T gamma delta lymphocytes. Immunol Today. 1989 Jun;10(6):186–188. doi: 10.1016/0167-5699(89)90321-6. [DOI] [PubMed] [Google Scholar]
  26. Wahab Z. A., Metzgar R. S. Human cytotoxic lymphocytes reactive with pancreatic adenocarcinoma cells. Pancreas. 1991 May;6(3):307–317. doi: 10.1097/00006676-199105000-00008. [DOI] [PubMed] [Google Scholar]
  27. Whiteside T. L., Miescher S., MacDonald H. R., Von Fliedner V. Separation of tumor-infiltrating lymphocytes from tumor cells in human solid tumors. A comparison between velocity sedimentation and discontinuous density gradients. J Immunol Methods. 1986 Jun 24;90(2):221–233. doi: 10.1016/0022-1759(86)90079-7. [DOI] [PubMed] [Google Scholar]
  28. Yoo Y. K., Heo D. S., Hata K., Van Thiel D. H., Whiteside T. L. Tumor-infiltrating lymphocytes from human colon carcinomas. Functional and phenotypic characteristics after long-term culture in recombinant interleukin 2. Gastroenterology. 1990 Feb;98(2):259–268. [PubMed] [Google Scholar]
  29. Zocchi M. R., Ferrarini M., Rugarli C. Selective lysis of the autologous tumor by delta TCS1+ gamma/delta+ tumor-infiltrating lymphocytes from human lung carcinomas. Eur J Immunol. 1990 Dec;20(12):2685–2689. doi: 10.1002/eji.1830201224. [DOI] [PubMed] [Google Scholar]

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

RESOURCES