Immunoprevalence and magnitude of HLA-DP4 versus HLA-DR-restricted spontaneous CD4+ Th1 responses against telomerase in cancer patients

ABSTRACTCumulative evidence supports that CD4+ Th1 cells play a key role in antitumor immunity. We previously reported the presence of spontaneous HLA-DR-restricted CD4+ Th1 responses against telomerase reverse transcriptase (TERT) in various cancers by using promiscuous HLA-DR epitopes. Here, we described novel highly immunogenic HLA-DP4-binding epitopes from TERT named TERT541–555, TERT573–587, TERT613–627 and TERT911–925 and addressed the question about the immunoprevalence and magnitude of the naturally occurring antitumor CD4+ T cell responses restricted by HLA-DP4 or HLA-DR, the two most common HLA class II. Direct comparative study of spontaneous anti-TERT CD4+ T cell responses in a cohort of 87 lung cancer patients showed that HLA-DP4 and HLA-DR sustained specific Th1 responses in 10.1% and 25.2% of cancer patients respectively (p = 0.01). The magnitude of the HLA-DR-restricted responses was two to three times significantly higher than HLA-DP one (p = 0.005). Similar results were found in other ca...