Patients selection [stratification] and then monitoring for immunotherapy effectiveness is part of precision medicine. In humans, especially, when determination of cancer neo-antigens is not always feasible, clinical diagnostic tests are focused on surrogate markers to tell whether patient has a tumor antigen-specific immune response. More recently, PD-1 has become one of such surrogate markers. However it is not clear whether expression of PD-1 could truly correlate with T cell antigen-specific response.
New paper in Journal Immunology provided data to suggest that at least in mice tumor models PD-1 expression does not correlate with T cell antigen-specific response within tumor tissue.
For example, they showed that OT-I CD8 T cells would express PD-1 irrespective whether tumor expresses or not specific OVA antigen. In contrast, Nur77 (part of TCR signaling) expression correlated with tumor neo-antigen expression.
This study indicate that diagnostic tests measuring PD-1 expression on tumor-infiltrating T cells may over-estimate tumor antigen-specific immune response and lead to unpredictable outcomes during antibody immunotherapy.