Immune checkpoint blockade augments lymphodepleting chemotherapy-induced antitumor immunity by expanding effector CD8+ T cell clones in preclinical models of cancer

Here, we show that a single dose of CTX one day prior to starting aPD-1+aCTLA-4 is sufficient to delay tumor progression in established melanoma and prolong survival in tumor-bearing mice in preclinical models. These effects extended to other lymphodepleting treatments, such as Gemcitabine and radiation therapy. The anti-tumor immune response was mainly driven by the clonal expansion of activated/effector CD8+ tumor infiltrating lymphocytes.

Furthermore, combined CTX and aPD-1+aCTLA-4 treatment demonstrated efficacy across additional preclinical tumor models, including colorectal cancer and triple negative breast cancer. Overall, our findings highlight that the combination of CTX and aPD-1+aCTLA-4 represents a clinically relevant approach in the treatment of ICB-refractory tumors.