These include combinations of two checkpoint inhibitors simultaneously targeting the PD-1, PD-L1, and CTLA-4 axes (or triple therapy with stereotactic radiation), combined with small molecule inhibitors (i.e., TGF-β receptor 1 kinase or Bruton tyrosine kinase (BTK) inhibitors), combined with an oncolytic virus, combined with chemokine antagonists, with CD40 agonists or with cancer vaccines. The gene discussed is BTK; the disease is cancer.