Specific immune recognition of autologous tumor by lymphocytes infiltrating colon carcinomas : analysis by cytokine secretion

Tumor-infiltrating lymphocytes (TIL) were grown in the presence of interleukin-2 from 19 colon carcinoma specimens, including 1 primary lesion and 18 metastatic lesions. These cultures showed a median proliferation of 606-fold (range 13-fold to 28,000-fold) over 49 culture days (range 26-76 days). B...

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Bibliographic Details
Published in:Cancer Immunology Immunotherapy 1993, Vol.36 (1), p.1-8
Main Authors: HOM, S. S, ROSENBERG, S. A, TOPALIAN, S. L
Format: Article
Language:English
Subjects:
Antineoplastic agents
Biological and medical sciences
Colonic Neoplasms - immunology
Colonic Neoplasms - pathology
Cytokines - metabolism
Cytotoxicity, Immunologic
Humans
Immunophenotyping
Immunotherapy
Killer Cells, Lymphokine-Activated
Lymphocyte Activation - physiology
Major Histocompatibility Complex
Medical sciences
Neoplasm Metastasis
Original
Pharmacology. Drug treatments
Tumor Cells, Cultured
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Summary:Tumor-infiltrating lymphocytes (TIL) were grown in the presence of interleukin-2 from 19 colon carcinoma specimens, including 1 primary lesion and 18 metastatic lesions. These cultures showed a median proliferation of 606-fold (range 13-fold to 28,000-fold) over 49 culture days (range 26-76 days). By phenotype, mature cultures were 69%-99% CD3+ (mean 93%) and contained mixed populations of CD4+ and CD8+ cells (CD4 > CD8 in 10 of 19 cultures). Fresh cryopreserved colon tumors were not lysed by autologous TIL in short-term 51Cr-release assays, and were poorly lysed by lymphokine-activated killer cells. Ten TIL cultures were assayed for cytokine secretion in response to autologous and allogeneic tumors during a 6- to 24-h coincubation. Culture supernatants were tested by ELISA for the presence of granulocyte/macrophage-colony-stimulating factor, interferon gamma, and tumor necrosis factor alpha. Of 10 TIL, 4 secreted at least two of these cytokines specifically in response to autologous and/or HLA-matched fresh allogeneic colon carcinomas, but not to melanomas or HLA-unmatched colon carcinomas. Cytokine secretion was mediated by both CD4+ and CD8+ TIL, and could be inhibited by mAb directed against the appropriate class of MHC antigen. These data provide evidence for specific, MHC-restricted immune recognition of human colon carcinomas by T lymphocytes.
ISSN:0340-7004
1432-0851
DOI:10.1007/BF01789124