Infiltration of tumors by systemically transferred tumor-reactive T lymphocytes is required for antitumor efficacy.
The systemic transfer of ex vivo-activated tumor-sensitized T lymphocytes can mediate immunologically specific regression of established tumors. However, it has not been conclusively established whether the infiltration of systemically transferred T cells into metastases is required for their effector function. In this study, T cells from lymph nodes draining the murine fibrosarcoma MCA 205 cells were activated ex vivo with anti-CD3 monoclonal antibody and interleukin-2. During the final 24 h of culture, the T cells were treated with pertussis toxin (PTX) to inhibit signaling through G protein-coupled chemokine receptors required for diapedesis. Systemically transferred PTX-treated cells did not have any therapeutic efficacy against 3-day established pulmonary metastases. This lack of efficacy correlated with their failure to infiltrate the tumor parenchyma. However, PTX-treated cells responded to tumor antigen stimulation with IFN-gamma secretion in vitro. More importantly, PTX-treated effector T cells prevented tumor growth when they were admixed with tumor cells and inoculated s.c. These results demonstrate that systemically transferred tumor-reactive T lymphocytes need to infiltrate the tumor parenchyma through the endothelium to initiate tumor regression, but PTX-sensitive proteins are not required for either antigen recognition or effector functions.
Mukai
S
S
Center for Surgery Research/FF50, The Cleveland Clinic Foundation, Ohio 44195, USA.
Kjaergaard
J
J
Shu
S
S
Plautz
G E
GE
D000818:Animals; D002465:Cell Movement; D005260:Female; D016219:Immunotherapy, Adoptive; D008175:Lung Neoplasms / Q000556:secondary; D051379:Mice; D008810:Mice, Inbred C57BL; D009374:Neoplasms, Experimental / Q000628:therapy*; D037342:Pertussis Toxin; D013601:T-Lymphocytes / Q000276:immunology* / Q000502:physiology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D010566:Virulence Factors, Bordetella; D037342:Pertussis Toxin