Sulforaphane Synergizes With PD‐1 Blockade Through Activating CD8 + T Cells in Non–Small Cell Lung Cancer: Preclinical and Clinical Investigations

ABSTRACT Anti‐PD‐1/PD‐L1 therapy has achieved promising success across several tumor types; however, its efficacy is still far from satisfactory in non–small cell lung cancer (NSCLC). Combining therapies have been attempted to synergize anti‐PD‐1/PD‐L1 therapy through activating antitumor response. Previously, we convinced the role of sulforaphane (SFN) in regulating tumor immune microenvironment (TME) to enhance antitumor response. Consistently, here we observed combining SFN with chemotherapy and anti‐PD‐1 therapy achieved the best tumor suppression versus other treatments in mouse models bearing Lewis lung carcinoma cells. Further, a clinical trial (KY‐2021‐0266) was performed, and the disease control and objective response rates were higher in the experimental group (SFN combined anti‐PD‐1 antibody and chemotherapy group, n = 30) compared with the control group (anti‐PD‐1 antibody combined chemotherapy group, n = 30) (100% vs. 93.3% and 86.7% vs. 60.0%, respectively). Moreover, the median progression‐free survival was longer (19 vs. 9.5 months, respectively) in the experimental group. After treatment, antitumor response was enriched, while CD8‐related function markers were elevated and myeloid‐derived suppressor cell/M2‐related markers were reduced in the experimental group. Two spurious progressions were observed in the experimental group. In conclusion, this synergistic effect suggests that SFN may be a promising immunosensitizer and a treatment option in NSCLC.