Checkpoint blockade immunotherapies can be extraordinarily effective, but might benefit only the minority of patients whose tumors are pre-infiltrated by T cells. Here, using lung adenocarcinoma mouse models, including genetic models, we show that autochthonous tumors that lacked T cell infiltration and resisted current treatment options could be successfully sensitized to host antitumor T cell immunity when appropriately selected immunogenic drugs (e.g., oxaliplatin combined with cyclophosphamide for treatment against tumors expressing oncogenic Kras and lacking Trp53) were used. The antitumor response was triggered by direct drug actions on tumor cells, relied on innate immune sensing through toll-like receptor 4 signaling, and ultimately depended on CD8+ T cell antitumor immunity. Furthermore, instigating tumor infiltration by T cells sensitized tumors to checkpoint inhibition and controlled cancer durably. These findings indicate that the proportion of cancers responding to checkpoint therapy can be feasibly and substantially expanded by combining checkpoint blockade with immunogenic drugs. Display omitted •Kras/Trp53 mutant tumors lack CD8+ T cells and resist chemo- and immunotherapies•Immunogenic chemotherapy elicits tumor T cell infiltration and controls cancer growth•Tumor control requires CD8+ T cells, TLR4+ cells, and drug actions on cancer cells•T cell influx sensitizes tumors to checkpoint inhibition and durably controls cancer There is an urgent need to expand the proportion of patients that respond to immune checkpoint therapy. Using clinically relevant genetic mouse models and a combination of immunogenic drugs to trigger T cell infiltration into tumors, Pittet and colleagues are able to make unresponsive tumors sensitive to checkpoint blockade therapy.