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Dominant rearrangements among human tumor‐infiltrating lymphocytes. Analysis of T‐cells derived from 32 patients with melanoma, lung, and renal cell carcinoma
Author(s) -
Bennett William T.,
Pandolfi Franco,
Grove Beverly H.,
Hawes Gail E.,
Boyle Lenora A.,
Kradin Richard L.,
Kurnick James T.
Publication year - 1992
Publication title -
cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 3.052
H-Index - 304
eISSN - 1097-0142
pISSN - 0008-543X
DOI - 10.1002/1097-0142(19920501)69:9<2379::aid-cncr2820690928>3.0.co;2-w
Subject(s) - t cell receptor , melanoma , tumor infiltrating lymphocytes , cd8 , cancer research , context (archaeology) , immunotherapy , carcinoma , gene rearrangement , t cell , pathology , medicine , biology , cancer , gene , immunology , antigen , immune system , genetics , paleontology
Abstract Dominant rearrangements of T‐cell receptor (TCR) β‐chain genes are reported among tumor‐infiltrating lymphocytes (TIL). After interleukin‐2 expansion of TIL from renal and lung carcinoma and melanoma biopsy tissues, rearrangements of TCR βchain genes were analyzed by Southern blotting. Nongermline restriction fragments, indicating dominant rearrangements, were detected among the TIL from all 6 patients with renal cell carcinoma, 17 of 20 patients with melanoma, and 3 of 6 patients with lung tumors. The restriction‐fragment sizes of these dominant rearrangements were heterogeneous among the various patients. Rearrangements into Cβ1 were more common than Cβ2 rearrangements. Phenotypic analyses indicated that dominant rearrangements occurred in both CD4 and CD8 predominant TIL populations. The TIL populations that were extracted were expanded to derive large cell numbers suitable for in vivo transfer in an interleukin‐2 and TIL immunotherapy program. The data indicated that the cells delivered to these patients usually were characterized by dominant populations of T‐cells with selective TCR gene rearrangements. The significance of selective TCR use requires evaluation of the function and specificity of the TIL comprising these dominant populations both in their native in vivo setting and in the context of therapeutic transfer.