Tumor-reactive CD4+ T cells develop cytotoxic activity and eradicate large established melanoma after transfer into lymphopenic hosts

• DOI: 10.1084/jem.20091918
• Publication Date: 2010-02-16T01:58:58Z
• Authors: Sergio A. Quezada; Tyler R. Simpson; Karl S. Peggs; Taha Merghoub; Jelena Vider; Xiaozhou Fan; Ronald Blasberg; Hideo Yagita; Pawel Muranski; Paul A. Antony; Nicholas P. Restifo; James P. Allison
• Keywords: Adoptive Cell Transfer

Adoptive transfer of large numbers tumor-reactive CD8+ cytotoxic T lymphocytes (CTLs) expanded and differentiated in vitro has shown promising clinical activity against cancer. However, such protocols are complicated by extensive ex vivo manipulations cells have largely focused on CTLs, with much less emphasis the role contribution CD4+ cells. Using a mouse model advanced melanoma, we found that small naive into lymphopenic recipients induces substantial cell expansion, differentiation, regression established tumors without need for manipulation. Surprisingly, developed activity, tumor rejection was dependent class II–restricted recognition Furthermore, blockade coinhibitory receptor CTL-associated antigen 4 (CTLA-4) transferred resulted greater expansion effector cells, diminished accumulation regulatory superior antitumor capable inducing spontaneous melanoma. These findings suggest novel potential therapeutic CTLA-4 cancer immunotherapy, demonstrate advantages differentiating over current favoring differentiation.