Growth and Functional Reactivity of Lymphocytes Obtained from Three Anatomic Compartments in Patients with Non–Small-Cell Lung Cancer (NSCLC)

Abstract

Non–small-cell lung cancer (NSCLC) claims the lives of both men and women worldwide. In this study, we describe the ability to expand lymphocytes from solid tumor biopsies, pleural fluid, and peripheral blood of patients with NSCLC. While lymphocytes readily expanded from both solid biopsies and pleural fluids, the incidence of obtaining tumor-specific lymphocytes was low. Specific cytolytic and/or cytokine-releasing activity was observed in tumor-infiltrating lymphocytes (TIL) from 3/15 solid tumor biopsies (20%) and 2 of 4 pleural fluid samples (50%). Two of the CTL derived from solid tumor were cytolytic, one being HLA-A2 restricted while the other was either restricted at HLA-A30 or - B18. One of the pleural fluid cytotoxic T lymphocyte (CTL) was also HLA-A2 restricted. Peripheral blood from NSCLC patients was studied using mixed lymphocyte tumor cell cultures (MLTC) as reported previously. Peripheral blood lymphocytes were cultured with allogeneic NSCLC-TC line 29.7, which expressed by gene transfer the lymphocyte costimulatory molecule CD80. Of 9 HLA-A2 patient samples tested, 8 gave rise to lymphocytes, which lysed NSCLC tumor cells expressing HLA-A2 in an major histocompatibility complex (MHC)–restricted fashion. While specific CTL can be generated from all anatomic sites, for clinical trials peripheral blood appears to be the site of choice for obtaining specific precursors.