Infiltration of tumors by systemically transferred tumor-reactive T lymphocytes is required for antitumor efficacy.
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| Abstract |
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.
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| Authors | S Mukai, J Kjaergaard, S Shu, G E Plautz |
| Journal | Cancer research (Cancer Res) Vol. 59 Issue 20 Pg. 5245-9 (Oct 15 1999) ISSN: 0008-5472 [Print] United States |
| PMID | 10537304 (Publication Type: Journal Article, Research Support, U.S. Gov't, P.H.S.) |
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