Anti-telomerase immune response predicts disease progression in chronic lymphocytic leukemia

Human telomerase reverse transcriptase (hTERT) is broadly expressed in many cancers. High hTERT expression have been described in chronic lymphocytic leukemia (CLL). Here we investigated the relationship between anti-hTERT immunity and disease progression in 49 CLL patients. Anti-hTERT T cell responses were evaluated by IFNγ-ELISpot. Complementary flow cytometry analyses were performed, and data were analyzed in regards of the treatment received by CLL patients afterward and disease progression. Anti-hTERT responses were more frequently observed in non-progressive watch and wait patients, and in progressive patients scheduled to receive ibrutinib, as compared to patients scheduled to receive other types of treatment. In vitro, addition of the anti-PD-1 antibody nivolumab increased anti-hTERT responses. Importantly, Kaplan Meier analyses showed significantly longer progression-free survival in patients with anti-hTERT immune responses at diagnosis as compared to non-responder patients. Our results show that anti-hTERT T cell responses represent a new potential biomarker predictive of CLL clinical outcome.