In addition to finding the most effective approach in RAS-RAF-MEK-ERK interference, the increased understanding of the impact of tumor-driven immune modulation and crosstalk with the TME has led to extensive investigational work on therapy regimens combining the immunomodulatory effects of MEKi with another selective inhibitor and an immunotherapeutic agent targeting immune checkpoint molecules (ICB), e.g., CTLA-4, PD-1 or PD-L1, or addressing immunostimulatory receptors, e.g., CD40, CD134 or CD137. The gene discussed is TNFRSF9; the disease is neoplasm.