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Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes. I. HLA-A2-restricted recognition of autologous and allogeneic tumor lines.
J Immunol. 1993 Oct 15; 151(8):4209-20.JI

Abstract

Metastatic renal cell carcinoma (RCC), like melanoma, belongs to the small group of human tumors in which partial or complete remission has been observed in some patients after treatment with various forms of immunotherapy. In contrast to melanoma, CTL showing MHC-restricted lysis of RCC have not been easily found among tumor-infiltrating lymphocytes (TIL). This has led to the suggestion by some that responses to immunotherapy are mediated predominantly by non-MHC-restricted effector cells. We have characterized an MHC-restricted, CD8+ CTL line obtained from an uncloned TIL population of a primary RCC using a low concentration of rIL-2; in fact, these CTL represented a majority of the short-term cultured TIL population. The CTL lysed autologous tumor cells but not normal kidney cells or target cells sensitive to non-MHC-restricted effector cells. In contrast, lymphokine-activated killer (LAK) cells grown in a high concentration of rIL-2 from the patient's PBL lysed autologous tumor and normal kidney cells in addition to several allogeneic tumors. The TIL could be expanded optimally using an autologous tumor line retrovirally transduced with the human cDNA encoding IL-2. TIL were 20-fold more potent than LAK cells in eliminating the IL-2 expressing tumor cells in vitro. The cultured TIL utilized a restricted number of V alpha gene families, suggesting that they may recognize only a limited number of MHC-peptide complexes presented by autologous tumor cells. HLA-A2 was identified as an MHC restriction molecule for presentation of one tumor-derived peptide to these CTL. Only some allogeneic HLA-A2 RCC tumors were lysed. Sequencing of the second and third exons of the HLA-A2 alleles of these cells revealed that both heterogeneity in MHC and peptide availability influenced CTL recognition. These studies demonstrate that some RCC express common antigenic determinants that can be recognized by MHC-restricted CTL and open the possibility of defining the nature of RCC-derived peptides, which, combined with HLA-A2, can generate specific immune responses.

Authors+Show Affiliations

Institut für Immunologie, Ludwig-Maximilians-Universität München, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

8409397

Citation

Schendel, D J., et al. "Tumor-specific Lysis of Human Renal Cell Carcinomas By Tumor-infiltrating Lymphocytes. I. HLA-A2-restricted Recognition of Autologous and Allogeneic Tumor Lines." Journal of Immunology (Baltimore, Md. : 1950), vol. 151, no. 8, 1993, pp. 4209-20.
Schendel DJ, Gansbacher B, Oberneder R, et al. Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes. I. HLA-A2-restricted recognition of autologous and allogeneic tumor lines. J Immunol. 1993;151(8):4209-20.
Schendel, D. J., Gansbacher, B., Oberneder, R., Kriegmair, M., Hofstetter, A., Riethmüller, G., & Segurado, O. G. (1993). Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes. I. HLA-A2-restricted recognition of autologous and allogeneic tumor lines. Journal of Immunology (Baltimore, Md. : 1950), 151(8), 4209-20.
Schendel DJ, et al. Tumor-specific Lysis of Human Renal Cell Carcinomas By Tumor-infiltrating Lymphocytes. I. HLA-A2-restricted Recognition of Autologous and Allogeneic Tumor Lines. J Immunol. 1993 Oct 15;151(8):4209-20. PubMed PMID: 8409397.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tumor-specific lysis of human renal cell carcinomas by tumor-infiltrating lymphocytes. I. HLA-A2-restricted recognition of autologous and allogeneic tumor lines. AU - Schendel,D J, AU - Gansbacher,B, AU - Oberneder,R, AU - Kriegmair,M, AU - Hofstetter,A, AU - Riethmüller,G, AU - Segurado,O G, PY - 1993/10/15/pubmed PY - 1993/10/15/medline PY - 1993/10/15/entrez SP - 4209 EP - 20 JF - Journal of immunology (Baltimore, Md. : 1950) JO - J. Immunol. VL - 151 IS - 8 N2 - Metastatic renal cell carcinoma (RCC), like melanoma, belongs to the small group of human tumors in which partial or complete remission has been observed in some patients after treatment with various forms of immunotherapy. In contrast to melanoma, CTL showing MHC-restricted lysis of RCC have not been easily found among tumor-infiltrating lymphocytes (TIL). This has led to the suggestion by some that responses to immunotherapy are mediated predominantly by non-MHC-restricted effector cells. We have characterized an MHC-restricted, CD8+ CTL line obtained from an uncloned TIL population of a primary RCC using a low concentration of rIL-2; in fact, these CTL represented a majority of the short-term cultured TIL population. The CTL lysed autologous tumor cells but not normal kidney cells or target cells sensitive to non-MHC-restricted effector cells. In contrast, lymphokine-activated killer (LAK) cells grown in a high concentration of rIL-2 from the patient's PBL lysed autologous tumor and normal kidney cells in addition to several allogeneic tumors. The TIL could be expanded optimally using an autologous tumor line retrovirally transduced with the human cDNA encoding IL-2. TIL were 20-fold more potent than LAK cells in eliminating the IL-2 expressing tumor cells in vitro. The cultured TIL utilized a restricted number of V alpha gene families, suggesting that they may recognize only a limited number of MHC-peptide complexes presented by autologous tumor cells. HLA-A2 was identified as an MHC restriction molecule for presentation of one tumor-derived peptide to these CTL. Only some allogeneic HLA-A2 RCC tumors were lysed. Sequencing of the second and third exons of the HLA-A2 alleles of these cells revealed that both heterogeneity in MHC and peptide availability influenced CTL recognition. These studies demonstrate that some RCC express common antigenic determinants that can be recognized by MHC-restricted CTL and open the possibility of defining the nature of RCC-derived peptides, which, combined with HLA-A2, can generate specific immune responses. SN - 0022-1767 UR - https://www.unboundmedicine.com/medline/citation/8409397/Tumor_specific_lysis_of_human_renal_cell_carcinomas_by_tumor_infiltrating_lymphocytes__I__HLA_A2_restricted_recognition_of_autologous_and_allogeneic_tumor_lines_ L2 - http://www.jimmunol.org/cgi/pmidlookup?view=long&pmid=8409397 DB - PRIME DP - Unbound Medicine ER -