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

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

  • Adv Sci (Weinh). 2022 Feb;9(5):e2103245. doi: 10.1002/advs.202103245.
Jung Min Shin 1 2,  Chan-Hyeong Lee 3,  Soyoung Son 1 4,  Chan Ho Kim 1,  Jae Ah Lee 1,  Hyewon Ko 5,  Sol Shin 4,  Seok Ho Song 1,  Seong-Sik Park 3,  Ju-Hyun Bae 3,  Ju-Mi Park 3,  Eun-Ji Choe 3,  Moon-Chang Baek 3,  Jae Hyung Park 1 4 6
Affiliations

Affiliations

  • 1 School of Chemical Engineering, College of Engineering, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Republic of Korea.
  • 2 Department of Genetic Resources, National Marine Biodiversity Institute of Korea (MABIK), 75 Jangsan-ro 101-gil, Janghang-eup, Seocheon, 33662, Republic of Korea.
  • 3 Department of Molecular Medicine, CMRI, Exosome Convergence Research Center (ECRC), School of Medicine, Kyungpook National University, Daegu, 41944, Republic of Korea.
  • 4 Department of Health Sciences and Technology, SAIHST, Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Republic of Korea.
  • 5 Bionanotechnology Research Center, Korea Research Institute of Bioscience & Biotechnology, 125 Gwahak-ro, Yuseong-gu, Daejeon, 34141, Republic of Korea.
  • 6 Biomedical Institute for Convergence at SKKU (BICS), Sungkyunkwan University, 2066 Seobu-ro, Jangan-gu, Suwon, 16419, Republic of Korea.
PMID: 34927389 DOI: 10.1002/advs.202103245
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.

Keywords

combination therapy; exosomal PD-L1; exosome; immune checkpoint therapy; immune escape; tumor microenvironment.

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