Abstract: The present invention relates to a method for diagnosis, prediction and/or prognosis of an active autoimmune pathology in a subject, comprising detecting the co-expression of PD-1 and CD38 proteins at the surface of T lymphocytes in a biological sample from the subject. The present invention also relates to a use of the pool of PD-1 (Programmed cell death 1) and CD38 protein as biomarkers for diagnosis, prediction and/or prognosis of an active autoimmune pathology in a subject.

Abstract: Targeting immune checkpoints, such as Programmed cell Death 1 (PD1), has improved survival in cancer patients by unleashing exhausted CD8+ T-cell thereby restoring anti-tumor immune responses. Most patients, however, relapse or are refractory to immune checkpoint blocking therapies. Here, the inventors show that NRP1 is recruited in the cytolytic synapse of PD1+CD8+ T-cells, interacts and enhances PD-1 activity. In mice, CD8+ T-cell specific deletion of Nrp1 improves spontaneous and anti PD1 antibody anti-tumor immune responses. Likewise, in human metastatic melanoma, the expression of NRP1 in tumor infiltrating CD8+ T-cells QI predicts poor outcome of patients treated with anti-PD1 (e.g. pembrolizumab). Finally, the combination of anti-NRP1 and anti-PD1 antibodies is synergistic in human, specifically in CD8+ T-cells anti-tumor response. Thus the therapeutic inhibition of NRP1 alone or combined with an immune checkpoint inhibitor (e.g.