Abstract
Activated tumor-infiltrating T lymphocytes (TIL-T) were quantitated prospectively in excisional biopsy specimens of 49 B-cell non-Hodgkin's lymphomas (NHL) of various grades and compared with eight benign lymphoid hyperplasias (BLH) to identify any potential difference in host T-cell response. Immunotyping of tissue-cell suspensions was done by three-color flow cytometry, which was complemented by immunocytology by using cytocentrifuged preparations. Two activated T-cell subsets were studied: acutely activated TIL-T (CD3+ CD25+ HLADr-) and chronically activated TIL-T (CD3+ CD25- HLADr+). Results showed an association of the more aggressive intermediate/high-grade B-cell NHL with a higher percentage of late-phase activated TIL-T and a progressive increase with the grade of malignancy: 10.29%, 23.25%, 33.87%, and 47.78% (means) for BLH and for low-, intermediate- and high-grade B-cell NHL, respectively. Differences for this subset were significant (P less than 0.050) for the following comparisons: hyperplasia versus intermediate-grade NHL (P less than 0.0012), hyperplasia versus high-grade NHL (P less than 0.0002), and low versus high-grade NHL (P less than 0.0080). The percentage of acutely activated TIL-T cells did not show a statistically significant difference between the groups. The results suggest a host T-cell response to proliferating neoplastic cells in B-cell NHL. Paradoxically, the response does not appear to be protective for the host since the intensity is directly proportional to the grade of malignancy. However, the recognition of this response may have clinical applications since its amplification with biological response modifiers may result in effective adoptive immunotherapy of B-cell NHL. Further clarification of the specificity and biologic significance of host T-cell activation in B-cell NHL will require functional studies of isolated lymphocytic subpopulations from neoplastic tissue.
Full text
PDF






Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Braylan R. C., Benson N. A. Flow cytometric analysis of lymphomas. Arch Pathol Lab Med. 1989 Jun;113(6):627–633. [PubMed] [Google Scholar]
- Bresnihan B., Jasin H. E. Suppressor function of peripheral blood mononuclear cells in normal individuals and in patients with systemic lupus erythematosus. J Clin Invest. 1977 Jan;59(1):106–116. doi: 10.1172/JCI108607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cozzolino F., Torcia M., Carossino A. M., Giordani R., Selli C., Talini G., Reali E., Novelli A., Pistoia V., Ferrarini M. Characterization of cells from invaded lymph nodes in patients with solid tumors. Lymphokine requirement for tumor-specific lymphoproliferative response. J Exp Med. 1987 Aug 1;166(2):303–318. doi: 10.1084/jem.166.2.303. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dvoretsky P., Wood G. S., Levy R., Warnke R. A. T-lymphocyte subsets in follicular lymphomas compared with those in non-neoplastic lymph nodes and tonsils. Hum Pathol. 1982 Jul;13(7):618–625. doi: 10.1016/s0046-8177(82)80003-8. [DOI] [PubMed] [Google Scholar]
- Finke J. H., Rayman P., Alexander J., Edinger M., Tubbs R. R., Connelly R., Pontes E., Bukowski R. Characterization of the cytolytic activity of CD4+ and CD8+ tumor-infiltrating lymphocytes in human renal cell carcinoma. Cancer Res. 1990 Apr 15;50(8):2363–2370. [PubMed] [Google Scholar]
- Gupta S. Autologous mixed lymphocyte reaction in health and disease states in man. Vox Sang. 1983;44(5):265–288. doi: 10.1111/j.1423-0410.1983.tb04483.x. [DOI] [PubMed] [Google Scholar]
- Hemler M. E., Jacobson J. G., Brenner M. B., Mann D., Strominger J. L. VLA-1: a T cell surface antigen which defines a novel late stage of human T cell activation. Eur J Immunol. 1985 May;15(5):502–508. doi: 10.1002/eji.1830150515. [DOI] [PubMed] [Google Scholar]
- Herberman R. B. Effects of biological response modifiers on effector cells with cytotoxic activity against tumors. Semin Oncol. 1986 Jun;13(2):195–199. [PubMed] [Google Scholar]
- Hsu S. M., Raine L., Fanger H. A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol. 1981 May;75(5):734–738. doi: 10.1093/ajcp/75.5.734. [DOI] [PubMed] [Google Scholar]
- Jacob M. C., Piccinni M. P., Bonnefoix T., Sotto M. F., Couderc P., Bensa J. C., Sotto J. J. T lymphocytes from invaded lymph nodes in patients with B-cell-derived non-Hodgkin's lymphoma: reactivity toward the malignant clone. Blood. 1990 Mar 1;75(5):1154–1162. [PubMed] [Google Scholar]
- Knowles D. M., 2nd, Halper J. P., Jakobiec F. A. T-lymphocyte subpopulations in B-cell-derived non-Hodgkin's lymphomas and Hodgkin's disease. Cancer. 1984 Aug 15;54(4):644–651. doi: 10.1002/1097-0142(1984)54:4<644::aid-cncr2820540410>3.0.co;2-a. [DOI] [PubMed] [Google Scholar]
- Lanier L. L., Loken M. R. Human lymphocyte subpopulations identified by using three-color immunofluorescence and flow cytometry analysis: correlation of Leu-2, Leu-3, Leu-7, Leu-8, and Leu-11 cell surface antigen expression. J Immunol. 1984 Jan;132(1):151–156. [PubMed] [Google Scholar]
- Lindemalm C., Mellstedt H., Biberfeld P., Björkholm M., Christensson B., Holm G., Johansson B., Sundblad R. Blood and lymph node T-lymphocyte subsets in non-Hodgkin lymphomas. Scand J Haematol. 1983 Jan;30(1):68–78. doi: 10.1111/j.1600-0609.1983.tb00636.x. [DOI] [PubMed] [Google Scholar]
- Loken M. R., Lanier L. L. Three-color immunofluorescence analysis of Leu antigens on human peripheral blood using two lasers on a fluorescence-activated cell sorter. Cytometry. 1984 Mar;5(2):151–158. doi: 10.1002/cyto.990050209. [DOI] [PubMed] [Google Scholar]
- Miller M. L., Tubbs R. R., Fishleder A. J., Savage R. A., Sebek B. A., Weick J. K. Immunoregulatory Leu-7+ and T8+ lymphocytes in B-cell follicular lymphomas. Hum Pathol. 1984 Sep;15(9):810–817. doi: 10.1016/s0046-8177(84)80141-0. [DOI] [PubMed] [Google Scholar]
- Oshimi K., Oshimi Y., Akutsu M., Takei Y., Saito H., Okada M., Mizoguchi H. Cytotoxicity of interleukin 2-activated lymphocytes for leukemia and lymphoma cells. Blood. 1986 Oct;68(4):938–948. [PubMed] [Google Scholar]
- Reinherz E. L., Kung P. C., Pesando J. M., Ritz J., Goldstein G., Schlossman S. F. Ia determinants on human T-cell subsets defined by monoclonal antibody. Activation stimuli required for expression. J Exp Med. 1979 Dec 1;150(6):1472–1482. doi: 10.1084/jem.150.6.1472. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reinherz E. L., Rubinstein A., Geha R. S., Strelkauskas A. J., Rosen F. S., Schlossman S. F. Abnormalities of immunoregulatory T cells in disorders of immune function. N Engl J Med. 1979 Nov 8;301(19):1018–1022. doi: 10.1056/NEJM197911083011902. [DOI] [PubMed] [Google Scholar]
- Reinherz E. L., Schlossman S. F. Current concepts in immunology: Regulation of the immune response--inducer and suppressor T-lymphocyte subsets in human beings. N Engl J Med. 1980 Aug 14;303(7):370–373. doi: 10.1056/NEJM198008143030704. [DOI] [PubMed] [Google Scholar]
- Ress S. R., Strassmann G., Bach F. H. HLA-DR expression on cytotoxic T lymphocytes. Scand J Immunol. 1985 Nov;22(5):455–461. doi: 10.1111/j.1365-3083.1985.tb01903.x. [DOI] [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]
- Sanders M. E., Makgoba M. W., Sharrow S. O., Stephany D., Springer T. A., Young H. A., Shaw S. Human memory T lymphocytes express increased levels of three cell adhesion molecules (LFA-3, CD2, and LFA-1) and three other molecules (UCHL1, CDw29, and Pgp-1) and have enhanced IFN-gamma production. J Immunol. 1988 Mar 1;140(5):1401–1407. [PubMed] [Google Scholar]
- Shackney S. E., Skramstad K. A dynamic interpretation of multiparameter studies in the lymphomas. Am J Clin Pathol. 1979 Oct;72(4 Suppl):756–764. [PubMed] [Google Scholar]
- Sheibani K., Tubbs R. R. Enzyme immunohistochemistry: technical aspects. Semin Diagn Pathol. 1984 Nov;1(4):235–250. [PubMed] [Google Scholar]
- Slovin S. F., Lackman R. D., Ferrone S., Kiely P. E., Mastrangelo M. J. Cellular immune response to human sarcomas: cytotoxic T cell clones reactive with autologous sarcomas. I. Development, phenotype, and specificity. J Immunol. 1986 Nov 1;137(9):3042–3048. [PubMed] [Google Scholar]
- Smith J. B., Knowlton R. P., Harris D. T. Functional aspects of T-cells from patients with non-Hodgkin's lymphoma. Responses to self, TNP-modified self, and alloantigens. Cancer. 1983 Oct 1;52(7):1160–1164. doi: 10.1002/1097-0142(19831001)52:7<1160::aid-cncr2820520706>3.0.co;2-g. [DOI] [PubMed] [Google Scholar]
- Vose B. M., Moore M. Human tumor-infiltrating lymphocytes: a marker of host response. Semin Hematol. 1985 Jan;22(1):27–40. [PubMed] [Google Scholar]
- Vánky F., Péterffy A., Bök K., Willems J., Klein E., Klein G. Correlation between lymphocyte-mediated auto-tumor reactivities and the clinical course. II. Evaluation of 69 patients with lung carcinoma. Cancer Immunol Immunother. 1983;16(1):17–22. doi: 10.1007/BF00199900. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Zimmermann R., Ozer H., DeWolf W. C., Evans R. L., Yunis E. J., Schlossman S. F. The detection of Ia-like and DRw antigens on activated T cells. Transplant Proc. 1979 Dec;11(4):1770–1773. [PubMed] [Google Scholar]
