CD4 + T-cell-Mediated Rejection of MHC Class II-Positive Tumor Cells Is Dependent on Antigen Secretion and Indirect Presentation on Host APCs

• Published in: Cancer research (Chicago, Ill.) Ill.), 2018-08, Vol.78 (16), p.4573-4585
• Main Authors: Haabeth, Ole Audun W, Fauskanger, Marte, Manzke, Melanie, Lundin, Katrin U, Corthay, Alexandre, Bogen, Bjarne, Tveita, Anders A
• Format: Article
• Language: English
• ISSN: 0008-5472; 1538-7445
• DOI: 10.1158/0008-5472.CAN-17-2426

Tumor-specific CD4 T cells have been shown to mediate efficient antitumor immune responses against cancer. Such responses can occur through direct binding to MHC class II (MHC II)-expressing tumor cells, or indirectly via activation of professional antigen-presenting cells (APC) that take up and present the tumor antigen. We have previously shown that CD4 T cells reactive against an epitope within the Ig light chain variable region of a murine B-cell lymphoma can reject established tumors. Given the presence of MHC II molecules at the surface of lymphoma cells, we investigated whether MHC II-restricted antigen presentation on tumor cells alone was required for rejection. Variants of the A20 B lymphoma cell line that either secreted or intracellularly retained different versions of the tumor-specific antigen revealed that antigen secretion by the MHC II-expressing tumor cells was essential both for the priming and effector phase of CD4 T-cell-driven antitumor immune responses. Consistent with this, genetic ablation of MHC II in tumor cells, both in the case of B lymphoma and B16 melanoma, did not preclude rejection of tumors by tumor antigen-specific CD4 T cells These findings demonstrate that MHC class II expression on tumor cells themselves is not required for CD4 T-cell-mediated rejection and that indirect display on host APC is sufficient for effective tumor elimination. These results support the importance of tumor-infiltrating APC as mediators of tumor cell killing by CD4 T cells. Elimination of tumors by CD4 T cells recognizing secreted tumor neoantigens can occur in the absence of tumor cell-intrinsic MHC II expression, highlighting the potential clinical relevance of indirect antigen recognition by tumor-infiltrating APC. http://cancerres.aacrjournals.org/content/canres/78/16/4573/F1.large.jpg .