The selection of the most-effective combinations of chemotherapy and immunotherapy can be challenging, owing to the immunosuppressive effects of certain forms of chemotherapy. Now, researchers have demonstrated that systemically administered carmustine results in severe and persistent lymphodepletion, while local delivery of the same drug from implanted polymers designed to release a constant dose of chemotherapy over a 2-week period left all measured immune-cell populations intact. A similar situation occurred following administration of anti-programmed cell death protein 1 (PD-1) antibodies: the effects of locally delivered carmustine synergized with those of the anti-PD-1 antibodies, whereas systemic chemotherapy resulted in lymphodepletion, thus abrogating the effects of PD-1 inhibition. These findings indicate a need to carefully consider effects on the immune system when designing combination regimens containing chemotherapy and immunotherapy.