Sulfisoxazole Elicits Robust Antitumour Immune Response Along with Immune Checkpoint Therapy by Inhibiting Exosomal PD-L1.

Abstract

Despite their potent antitumor activity, clinical application of immune checkpoint inhibitors has been significantly limited by their poor response rates (<30%) in cancer patients, primarily due to immunosuppressive tumor microenvironments. As a representative immune escape mechanism, cancer-derived exosomes have recently been demonstrated to exhaust CD8+ cytotoxic T cells. Here, it is reported that sulfisoxazole, a sulfonamide antibacterial, significantly decreases the exosomal PD-L1 level in blood when orally administered to the tumor-bearing mice. Consequently, sulfisoxazole effectively reinvigorates exhausted T cells, thereby eliciting robust antitumor effects in combination with anti-PD-1 antibody. Overall, sulfisoxazole regulates immunosuppression through the inhibition of exosomal PD-L1, implying its potential to improve the response rate of anti-PD-1 antibodies.

• Authors: Jung Min Shin, Chan-Hyeong Lee, Soyoung Son, Chan Ho Kim, Jae Ah Lee, Hyewon Ko, Sol Shin, Seok Ho Song, Seong-Sik Park, Ju-Hyun Bae, Ju-Mi Park, Eun-Ji Choe, Moon-Chang Baek, Jae Hyung Park
• Journal: Advanced science (Weinheim, Baden-Wurttemberg, Germany) (Adv Sci (Weinh)) Vol. 9 Issue 5 Pg. e2103245 (02 2022) ISSN: 2198-3844 [Electronic] Germany
• PMID: 34927389 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2021 The Authors. Advanced Science published by Wiley-VCH GmbH.

Chemical References

• B7-H1 Antigen
• Immune Checkpoint Inhibitors
• Sulfisoxazole

Topics

• Animals
• B7-H1 Antigen (antagonists & inhibitors)
• Exosomes (drug effects, immunology)
• Humans
• Immune Checkpoint Inhibitors (pharmacology, therapeutic use)
• Immunity
• Mice
• Neoplasms (drug therapy)
• Sulfisoxazole (pharmacology, therapeutic use)
• Tumor Microenvironment (drug effects)