These therapies block the immunoinhibitory receptor PD-1, which is normally expressed on the surface of activated T cells, regulatory T cells, B cells and natural killer (NK) cells 3, 6, 7. Accordingly, anti-PD-1 therapies (e.g., nivolumab) are based on improving the anti-tumor immune response against cancer cells, principally by stimulating the infiltrating cytotoxic T lymphocytes (CD8+) in the tumor microenvironment 5, 6, 7. Several of the most studied immune checkpoint targets, such as programmed cell death protein-1/programmed death ligand-1 (PD-1/PD-L1 axis), are involved in escape mechanisms from immunosurveillance 2, 3, 4. Thus, while keeping in mind that more research is needed to corroborate our findings, we report preliminary evidence for a previously undescribed immunotherapy mechanism in this model, suggesting a potential cytotoxic action of neutrophils as PD-1 inhibitor effector cells responsible for tumor regression by necrotic extension.Ĭancer immunotherapy, in particular antibody-based immune checkpoint blockers, represents a revolution in cancer treatment, generating unprecedented results in terms of overall and progression-free survival 1, 2. Indeed, anti-PD-1 treatment induced myeloid cell mobilization to the tumor concomitant with the production of exudates compatible with an acute inflammatory reaction mediated by murine polymorphonuclear leukocytes, specifically neutrophils. An antitumor effect was observed in animals that received anti-PD-1 treatment, alone or in combination with cisplatin, likely due to a mechanism independent of T lymphocytes. We used a murine patient-derived xenograft (PDX) model of early-stage non–small cell lung carcinoma (NSCLC) devoid of host lymphoid cells, and studied the tumor and immune non-lymphoid responses to immunotherapy with anti-PD-1 alone or in combination with standard chemotherapy (cisplatin). The purpose of this study was to investigate whether anti-PD-1 immunotherapy acts on malignant tumor cells through mechanisms beyond those related to T lymphocyte involvement. Nonetheless, not all patients benefit equally and many issues remain unresolved, including the mechanisms of action and the possible effector function of immune cells from non-lymphoid lineages. Immunotherapies, such as checkpoint blockade of programmed cell death protein-1 (PD-1), have resulted in unprecedented improvements in survival for patients with lung cancer.
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