Limiting dilution analysis of peripheral blood lymphocytes reacting with non-small-cell lung cancer: functionally heterogeneous effectors efficiently lyse autologous cancer cells.
It has recently been shown that the infusion of tumor infiltrating lymphocytes (TIL) and recombinant interleukin-2 (rIL-2) in patients operated on for advanced non-small-cell lung cancer (NSCLC), has significant effects in terms of the survival time and control of local relapses. Despite the evident clinical effects, the treatment is unavailable for patients in which TIL have lost their proliferative potential. In an attempt to identify new sources of effector cells using mixed lymphocyte/tumor cultures (MLTC), populations of peripheral blood (PB) lymphoid cells, which have the capability of lysing autologous NSCLC, were studied at the clonal level. Specific cytolytic lymphocytes were detected at very low frequencies in two out of four patients, whereas non-MHC restricted cytolytic T cells were frequently detected. Cytolytic CD4+ belonged to the Th0 or Th2 subsets and were characterized by cytokine secretion patterns suggestive of a lymphokine cascade that could be involved in cancer control. The identification of different efficient effector mechanisms at the clonal level strongly supports the use of in vitro activated lymphocytes, derived from PB, in protocols of adoptive immunotherapy in patients with advanced NSCLC in which TIL are unavailable.
Semino
C
C
Servizio di Patologia Clinica, Centro di Biotecnologie Avanzate, Istituto Nazionale per la Ricerca sul Cancro, Genova, Italy.
Cilli
M
M
Ratto
G B
GB
Deng
W
W
Pietra
G
G
Cangemi
G
G
Melioli
G
G
D000368:Aged; D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000276:immunology / Q000628:therapy*; D016207:Cytokines / Q000378:metabolism*; D006801:Humans; D007201:Indicator Dilution Techniques; D008175:Lung Neoplasms / Q000276:immunology / Q000628:therapy*; D008214:Lymphocytes / Q000378:metabolism*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D014407:Tumor Cells, Cultured
D016207:Cytokines