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). 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.
Hom
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Division of Cancer Treatment, National Cancer Institute, National Institutes of Health, Bethesda, Maryland 20892.
Rosenberg
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SA
Topalian
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SL
D003110:Colonic Neoplasms / Q000276:immunology* / Q000473:pathology; D016207:Cytokines / Q000378:metabolism*; D003602:Cytotoxicity, Immunologic; D006801:Humans; D016130:Immunophenotyping; D015979:Killer Cells, Lymphokine-Activated; D008213:Lymphocyte Activation / Q000502:physiology*; D008285:Major Histocompatibility Complex; D009362:Neoplasm Metastasis; D014407:Tumor Cells, Cultured
D016207:Cytokines