Precision oncology has emerged as a major focus of cancer therapeutics. This strategy is based on the hope that therapy tailored to the specific molecular features of a patient’s cancer will yield superior results, compared with the traditional “one-size-fitsall” therapeutic approach (1). Similarly, modern immunotherapeutic approaches aim to take advantage of establishing a tumor-specific immune response that will eradicate tumor cells within an individual patient and provide lasting antitumor immune memory (2).

Despite promising advances in precision oncology, hypoxia (defined here as partial pressure of oxygen [pO2]< 10 mmHg) remains a significant barrier to therapeutic efficacy. Small molecule–targeted agents are susceptible to cellular drug resistance mechanisms, including mechanisms driven by hypoxia (3, 4). Spatial and temporal variation in tumor hypoxia (5) may contribute to the heterogeneity in treatment response to precision oncology drug combinations (1). Hypoxia influences efficacy of immunotherapy via several mechanisms, including both innate and adaptive immunity. For example, hypoxia promotes polarization of macrophages toward the immunosuppressive M2 phenotype (6) and affects NK cell function by reducing expression of the activating receptor NKG2D (7). With respect to the adaptive immune system, hypoxia disturbs the balance between effector T cells and immunosuppressive regulatory T cells (8). Hypoxia also interferes with immune checkpoint balance by decreasing MHC class I expression by tumor cells (9), increasing programmed death ligand 1 (PD-L1) expression via the HIF-1 pathway, and promoting secretion of immunosuppressive cytotoxic T lympho-