Research Papers:

Enhanced expression of PD-L1 in non-muscle-invasive bladder cancer after treatment with Bacillus Calmette-Guerin

Akihito Hashizume, Susumu Umemoto, Tomoyuki Yokose, Yoshiyasu Nakamura, Mitsuyo Yoshihara, Kahori Shoji, Satoshi Wada, Yohei Miyagi, Takeshi Kishida and Tetsuro Sasada _

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Oncotarget. 2018; 9:34066-34078. https://doi.org/10.18632/oncotarget.26122

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Akihito Hashizume1, Susumu Umemoto1, Tomoyuki Yokose2, Yoshiyasu Nakamura3, Mitsuyo Yoshihara3, Kahori Shoji3, Satoshi Wada3,4, Yohei Miyagi3, Takeshi Kishida1 and Tetsuro Sasada3,4

1Department of Urology, Kanagawa Cancer Center, Yokohama, Japan

2Department of Pathology, Kanagawa Cancer Center, Yokohama, Japan

3Kanagawa Cancer Center Research Institute, Yokohama, Japan

4Cancer Vaccine Center, Kanagawa Cancer Center, Yokohama, Japan

Correspondence to:

Tetsuro Sasada, email: [email protected]

Takeshi Kishida, email: [email protected]

Keywords: PD-L1; non-muscle-invasive bladder cancer; Bacillus Calmette-Guerin; CD8; immune checkpoint

Received: May 01, 2018    Accepted: September 01, 2018    Published: September 25, 2018


Immune checkpoint molecules, such as PD-1/PD-L1, are reported to be closely associated with suppression of antitumor immunity, and their inhibitors have been used to treat various cancers including bladder cancer. However, there have been only a few studies investigating the effects of Bacillus Calmette-Guerin (BCG) administration on expression of the immune checkpoint molecules in bladder cancer. The current study examined the expression of PD-L1 and PD-L2 before and after BCG in non-muscle-invasive bladder cancer (NMIBC) patients. Tissue microarrays of 22 BCG-resistant NMIBC patients were stained by immunohistochemistry with antibodies against PD-L1, PD-L2, and CD8, and were compared between before and after BCG. The expression levels of PD-L1, but not of PD-L2, were significantly increased after BCG treatment on tumor cells (p < 0.001) and tumor-infiltrating inflammatory cells (p = 0.030) within tumor tissues, as well as on inflammatory cells within non-tumor normal tissues (p = 0.003). Although CD8+ T cells were significantly increased within tumor tissues (p = 0.005) and non-tumor normal tissues (p = 0.007) after BCG treatment, they might be not effective for anti-tumor immunity. This study demonstrated for the first time that expression of PD-L1, which might contribute to the immune escape mechanism, was enhanced on tumor tissue after BCG treatment in BCG-resistant NMIBC patients. Our finding thus propose that immunotherapy with anti-PD-1/PD-L1 antibodies could be feasible as combination treatment with BCG or as secondary treatment at relapse after BCG in NMIBC patients.

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