<i>Clostridium butyricum</i> therapy restores the decreased efficacy of immune checkpoint blockade in lung cancer patients receiving proton pump inhibitors
Yusuke Tomita, Yoshihiko Goto, Shinya Sakata, Kosuke Imamura, Ayaka Minemura, Kentaro Oka, Atsushi Hayashi, Takayuki Jodai, Kimitaka Akaike, Moriyasu Anai, Shohei Hamada, Shinji Iyama, Koichi Saruwatari, Sho Saeki, Motomichi Takahashi, Tokunori Ikeda, Takuro Sakagami
Abstract
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.