Interleukin-34 cancels anti-tumor immunity by PARP inhibitor
- Author:
Takayoshi NAKAMURA
1
;
Nabeel KAJIHARA
;
Naoki HAMA
;
Takuto KOBAYASHI
;
Ryo OTSUKA
;
Nanumi HAN
;
Haruka WADA
;
Yoshinori HASEGAWA
;
Nao SUZUKI
;
Ken-ichiro SEINO
Author Information
- Publication Type:Original Article
- From:Journal of Gynecologic Oncology 2023;34(3):e25-
- CountryRepublic of Korea
- Language:English
-
Abstract:
Objective:Breast cancer susceptibility gene 1 (BRCA1)-associated ovarian cancer patients have been treated with A poly (ADP-ribose) polymerase (PARP) inhibitor, extending the progression-free survival; however, they finally acquire therapeutic resistance. Interleukin (IL)-34 has been reported as a poor prognostic factor in several cancers, including ovarian cancer, and it contributes to the therapeutic resistance of chemotherapies. IL-34 may affect the therapeutic effect of PARP inhibitor through the regulation of tumor microenvironment (TME).
Methods:In this study, The Cancer Genome Atlas (TCGA) data set was used to evaluate the prognosis of IL-34 and human ovarian serous carcinoma. We also used CRISPR-Cas9 genome editing technology in a mouse model to evaluate the efficacy of PARP inhibitor therapy in the presence or absence of IL-34.
Results:We found that IL34 was an independent poor prognostic factor in ovarian serous carcinoma, and its high expression significantly shortens overall survival. Furthermore, in BRCA1-associated ovarian cancer, PARP inhibitor therapy contributes to anti-tumor immunity via the XCR1+ DC-CD8+ T cell axis, however, it is canceled by the presence of IL-34.
Conclusion:These results suggest that tumor-derived IL-34 benefits tumors by creating an immunosuppressive TME and conferring PARP inhibitor therapeutic resistance. Thus, we showed the pathological effect of IL-34 and the need for it as a therapeutic target in ovarian cancer.
