In particular, targeting the CAFs or their secretome may probably not induce a complete tumor cell death by itself, but it will help to reduce immune effector cell dysfunctions as well as the recruitment of immunosuppressive cells, thus releasing the “brake” for a more effective immune response in combination with therapy targeting immune checkpoints (e.g., anti-CTLA4, anti-PD1/PD-L1 antibodies) or other mechanisms impairing the anti-tumor immune response in patients (199). The gene discussed is CTLA4; the disease is neoplasm.