Evidence for in situ expansion of diverse antitumor-specific cytotoxic T lymphocyte clones in a human large cell carcinoma of the lung

We have isolated several cytotoxic T lymphocyte (CTL) clones from lymphocyt es infiltrating a human large cell carcinoma (LCC) of the lung. All these c lones were found to express a CD3(+) TCR alpha beta(+), CD8(+), CD4(-), CD2 8(-) phenotype, According to their TCR beta chain variable region expressio n, they were divided in three major groups. The first group, including the majority of the clones, expressed a unique V(beta)3-J(beta)1.2 TCR, The sec ond group expressed a V(beta)22-J(beta)1.4 rearrangement and the third grou p, including only two clones, expressed a V(beta)8-J(beta)1.5 TCR, Function al studies showed that all the CTL clones mediated a high cytotoxic activit y against the autologous tumor cell line, While the V(beta)3(+) clones show ed a weak lysis against few allogeneic nonsmall cell lung cancer (NSCLC) tu mor cell lines, V(beta)8(+) and V(beta)22(+) T cell clones were able to kil l a panel of allogeneic NSCLC tumor cell lines. Cytotoxicity-blocking exper iments using specific mAb indicated that, while the V(beta)3(+) and V(beta) 22(+) CTL clones were HLA-AS restricted, the V(beta)8(+) clones appeared HL A-B or -C restricted. TCR transcripts expressed in the cloned cells were de termined by CDR3 size and sequence analyses, and compared to those present in fresh tumor tissue. Interestingly, our studies demonstrated that the CTL clones identified in vitro were selectively expanded in vivo at the tumor site as compared to autologous peripheral blood lymphocytes. These results further provide evidence that an immune response may take place in NSCLC an d that effector T cells may contribute to tumor regression.