In summary, we show anti-N1 is well tolerated in mice harboring melanoma tumors; it does not cause GI-associated side effects alone or in combination with anti-PD-1; and importantly, exerts significant anti-tumor activity as monotherapy, partly by increasing tumor CD8+ T cell cytotoxicity, explaining why anti-N1 boosts anti-PD-1 therapy. The gene discussed is PDCD1; the disease is melanoma.