Abstract
In this paper we investigate the reactivity pattern of T cells from stomach carcinoma patients against autologous tumour cells. T cells obtained from the tumour environment, tumour-draining lymph nodes and peripheral blood were cloned in 78 patients with stomach cancer and anti-tumour cytotoxic T lymphocytes (CTLs) precursor frequencies were assessed in each sample by using limiting dilution analysis. When tumour-specific CTLs were tested for specific T-cell killing by using only low doses of Interleukin 2 (100 U ml-1), a moderate rate of proliferation frequency of T cells (0.047) and specific cytotoxicity (12%) were observed in lymph node populations. When both IL-2 and autologous tumour cells in mixed lymphocyte tumour cultures (MLTCs) were used for stimulation, a dramatic increase in number (0.1) and in specific lytic activity (46%) could be measured. No effect or specific activity to tumour cells was observed with peripheral blood lymphocytes and tumour-infiltrating lymphocytes.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Anichini A., Mazzocchi A., Fossati G., Parmiani G. Cytotoxic T lymphocyte clones from peripheral blood and from tumor site detect intratumor heterogeneity of melanoma cells. Analysis of specificity and mechanisms of interaction. J Immunol. 1989 May 15;142(10):3692–3701. [PubMed] [Google Scholar]
- Belldegrun A., Muul L. M., Rosenberg S. A. Interleukin 2 expanded tumor-infiltrating lymphocytes in human renal cell cancer: isolation, characterization, and antitumor activity. Cancer Res. 1988 Jan 1;48(1):206–214. [PubMed] [Google Scholar]
- Correa P. Clinical implications of recent developments in gastric cancer pathology and epidemiology. Semin Oncol. 1985 Mar;12(1):2–10. [PubMed] [Google Scholar]
- Floutsis G., Ulsh L., Ladisch S. Immunosuppressive activity of human neuroblastoma tumor gangliosides. Int J Cancer. 1989 Jan 15;43(1):6–9. doi: 10.1002/ijc.2910430103. [DOI] [PubMed] [Google Scholar]
- Gervois N., Heuze F., Diez E., Jotereau F. Selective expansion of a specific anti-tumor CD8+ cytotoxic T lymphocyte clone in the bulk culture of tumor-infiltrating lymphocytes from a melanoma patient: cytotoxic activity and T cell receptor gene rearrangements. Eur J Immunol. 1990 Apr;20(4):825–831. doi: 10.1002/eji.1830200417. [DOI] [PubMed] [Google Scholar]
- 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]
- Itoh K., Tilden A. B., Balch C. M. Interleukin 2 activation of cytotoxic T-lymphocytes infiltrating into human metastatic melanomas. Cancer Res. 1986 Jun;46(6):3011–3017. [PubMed] [Google Scholar]
- Kuppner M. C., Hamou M. F., Sawamura Y., Bodmer S., de Tribolet N. Inhibition of lymphocyte function by glioblastoma-derived transforming growth factor beta 2. J Neurosurg. 1989 Aug;71(2):211–217. doi: 10.3171/jns.1989.71.2.0211. [DOI] [PubMed] [Google Scholar]
- Kuppner M. C., Sawamura Y., Hamou M. F., de Tribolet N. Influence of PGE2- and cAMP-modulating agents on human glioblastoma cell killing by interleukin-2-activated lymphocytes. J Neurosurg. 1990 Apr;72(4):619–625. doi: 10.3171/jns.1990.72.4.0619. [DOI] [PubMed] [Google Scholar]
- McLemore T. L., Hubbard W. C., Litterst C. L., Liu M. C., Miller S., McMahon N. A., Eggleston J. C., Boyd M. R. Profiles of prostaglandin biosynthesis in normal lung and tumor tissue from lung cancer patients. Cancer Res. 1988 Jun 1;48(11):3140–3147. [PubMed] [Google Scholar]
- Miescher S., Stoeck M., Qiao L., Barras C., Barrelet L., von Fliedner V. Preferential clonogenic deficit of CD8-positive T-lymphocytes infiltrating human solid tumors. Cancer Res. 1988 Dec 15;48(24 Pt 1):6992–6998. [PubMed] [Google Scholar]
- Miescher S., Stoeck M., Qiao L., Barras C., Barrelet L., von Fliedner V. Proliferative and cytolytic potentials of purified human tumor-infiltrating T lymphocytes. Impaired response to mitogen-driven stimulation despite T-cell receptor expression. Int J Cancer. 1988 Nov 15;42(5):659–666. doi: 10.1002/ijc.2910420504. [DOI] [PubMed] [Google Scholar]
- Miescher S., Whiteside T. L., Carrel S., von Fliedner V. Functional properties of tumor-infiltrating and blood lymphocytes in patients with solid tumors: effects of tumor cells and their supernatants on proliferative responses of lymphocytes. J Immunol. 1986 Mar 1;136(5):1899–1907. [PubMed] [Google Scholar]
- Miescher S., Whiteside T. L., Moretta L., von Fliedner V. Clonal and frequency analyses of tumor-infiltrating T lymphocytes from human solid tumors. J Immunol. 1987 Jun 1;138(11):4004–4011. [PubMed] [Google Scholar]
- Moretta A., Pantaleo G., Moretta L., Cerottini J. C., Mingari M. C. Direct demonstration of the clonogenic potential of every human peripheral blood T cell. Clonal analysis of HLA-DR expression and cytolytic activity. J Exp Med. 1983 Feb 1;157(2):743–754. doi: 10.1084/jem.157.2.743. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Mukherji B., Nashed A. L., Guha A., Ergin M. T. Regulation of cellular immune response against autologous human melanoma. II. Mechanism of induction and specificity of suppression. J Immunol. 1986 Mar 1;136(5):1893–1898. [PubMed] [Google Scholar]
- Mukherji B., Wilhelm S. A., Guha A., Ergin M. T. Regulation of cellular immune response against autologous human melanoma. I. Evidence for cell-mediated suppression of in vitro cytotoxic immune response. J Immunol. 1986 Mar 1;136(5):1888–1892. [PubMed] [Google Scholar]
- Mukhopadhyaya R., Tatake R. J., Krishnan N., Rao R. S., Fakih A. R., Naik S. L., Gangal S. G. Immunoreactivity of lymphocytes from draining lymph nodes, peripheral blood and tumor infiltrates from oral cancer patients. J Clin Lab Immunol. 1989 Sep;30(1):21–25. [PubMed] [Google Scholar]
- 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]
- Nagarkatti M., Clary S. R., Nagarkatti P. S. Characterization of tumor-infiltrating CD4+ T cells as Th1 cells based on lymphokine secretion and functional properties. J Immunol. 1990 Jun 15;144(12):4898–4905. [PubMed] [Google Scholar]
- Nakamura H., Ishiguro K., Mori T. Different immune functions of peripheral blood, regional lymph node, and tumor infiltrating lymphocytes in lung cancer patients. Cancer. 1988 Dec 15;62(12):2489–2497. doi: 10.1002/1097-0142(19881215)62:12<2489::aid-cncr2820621207>3.0.co;2-j. [DOI] [PubMed] [Google Scholar]
- North R. J. Down-regulation of the antitumor immune response. Adv Cancer Res. 1985;45:1–43. doi: 10.1016/s0065-230x(08)60265-1. [DOI] [PubMed] [Google Scholar]
- Rabinowich H., Cohen R., Bruderman I., Steiner Z., Klajman A. Functional analysis of mononuclear cells infiltrating into tumors: lysis of autologous human tumor cells by cultured infiltrating lymphocytes. Cancer Res. 1987 Jan 1;47(1):173–177. [PubMed] [Google Scholar]
- 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]
- Slocum H. K., Pavelic Z. P., Rustum Y. M., Creaven P. J., Karakousis C., Takita H., Greco W. R. Characterization of cells obtained by mechanical and enzymatic means from human melanoma, sarcoma, and lung tumors. Cancer Res. 1981 Apr;41(4):1428–1434. [PubMed] [Google Scholar]
- Taswell C. Limiting dilution assays for the determination of immunocompetent cell frequencies. I. Data analysis. J Immunol. 1981 Apr;126(4):1614–1619. [PubMed] [Google Scholar]
- Taswell C., MacDonald H. R., Cerottini J. C. Clonal analysis of cytolytic T lymphocyte specificity. I. Phenotypically distinct sets of clones as the cellular basis of cross-reactivity to alloantigens. J Exp Med. 1980 Jun 1;151(6):1372–1385. doi: 10.1084/jem.151.6.1372. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tatake R. J., Krishnan N., Rao R. S., Fakih A. R., Gangal S. G. Lymphokine-activated killer-cell function of lymphocytes from peripheral blood, regional lymph nodes and tumor tissues of patients with oral cancer. Int J Cancer. 1989 Apr 15;43(4):560–566. doi: 10.1002/ijc.2910430405. [DOI] [PubMed] [Google Scholar]
- Topalian S. L., Solomon D., Rosenberg S. A. Tumor-specific cytolysis by lymphocytes infiltrating human melanomas. J Immunol. 1989 May 15;142(10):3714–3725. [PubMed] [Google Scholar]
- Uchida A., Moore M., Klein E. Autologous mixed lymphocyte-tumor reaction and autologous mixed lymphocyte reaction. II. Generation of specific and non-specific killer T cells capable of lysing autologous tumor. Int J Cancer. 1988 May 15;41(5):651–656. doi: 10.1002/ijc.2910410502. [DOI] [PubMed] [Google Scholar]
- Vose B. M. Quantitation of proliferative and cytotoxic precursor cells directed against human tumours: limiting dilution analysis in peripheral blood and at the tumour site. Int J Cancer. 1982 Aug 15;30(2):135–142. doi: 10.1002/ijc.2910300202. [DOI] [PubMed] [Google Scholar]
- Whiteside T. L., Miescher S., Hurlimann J., Moretta L., von Fliedner V. Separation, phenotyping and limiting dilution analysis of T-lymphocytes infiltrating human solid tumors. Int J Cancer. 1986 Jun 15;37(6):803–811. doi: 10.1002/ijc.2910370602. [DOI] [PubMed] [Google Scholar]
- Wölfel T., Klehmann E., Müller C., Schütt K. H., Meyer zum Büschenfelde K. H., Knuth A. Lysis of human melanoma cells by autologous cytolytic T cell clones. Identification of human histocompatibility leukocyte antigen A2 as a restriction element for three different antigens. J Exp Med. 1989 Sep 1;170(3):797–810. doi: 10.1084/jem.170.3.797. [DOI] [PMC free article] [PubMed] [Google Scholar]
- 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]
