Oral microbiota is associated with human diseases including cancer. Emerging evidence suggests that proton pump inhibitors (PPIs), which allow the oral microbiome to translocate into the gut, negatively influence the efficacy of immune checkpoint blockade (ICB) in cancer patients. However, currently there is no effective treatment that restores the decreased efficacy. To address this issue, we retrospectively evaluated 118 advanced or recurrent non-small cell lung cancer (NSCLC) patients treated with ICB and analyzed 80 fecal samples of patients with lung cancer by 16S metagenomic sequencing. Clostridium butyricum therapy using C. butyricum MIYAIRI 588 (CBM588), a live biotherapeutic bacterial strain, was shown to improve the ICB efficacy in lung cancer. Thus, we investigated how CBM588 affects the efficacy of ICB and the gut microbiota of lung cancer patients undergoing PPI treatment. We found that PPI treatment significantly decreased the efficacy of ICB in NSCLC patients, however, CBM588 significantly restored the diminished efficacy of ICB and improved survival. In addition, CBM588 prolonged overall survival in patients receiving PPIs and antibiotics together. The fecal analysis revealed that PPI users had higher abundance of harmful oral-related pathobionts and lower abundance of beneficial gut bacteria for immunotherapy. In contrast, patients who received CBM588 had lesser relative abundance of potentially harmful oral-related bacteria in the gut. Our research suggests that manipulating commensal microbiota by CBM588 may improve the therapeutic efficacy of ICB in cancer patients receiving PPIs, highlighting the potential of oral-related microbiota in the gut as a new therapeutic target for cancer immunotherapy.

Sebaceous carcinoma is a rare cutaneous malignant tumor, usually occurring on the eyelids, head, neck, and trunk. There have been few reports about sebaceous carcinoma with primary lung cancer, for which optimal therapy has not yet been established. A 70‐year‐old man presented with a mass in the left iliac bone and tumor of the lower left lung. The morphological characteristics of the iliac bone biopsy pathology and immunostaining results showed sebaceous gland differentiation. After systemic examination, we diagnosed a primary lung sebaceous carcinoma with intrapulmonary and bone metastases. PD‐L1 was positive in 1%–24% of tumor cells, and microsatellites were stable. We detected protein kinase B (AKT1) mutations using the Oncomine Dx target test. Palliative radiotherapy (RT) of a total of 45 Gy was provided in 15 fractions to the left iliac region, which resulted in a 25% reduction in the tumor size. Subsequently, four courses of first‐line pembrolizumab led to a 30% reduction in the total tumor count. RT and pembrolizumab may be treatment options for certain rare primary sebaceous carcinomas of the lungs. A synergistic effect from RT and subsequent administration of immune checkpoint inhibitors may have contributed to tumor reduction.