Targeting CD73 increases therapeutic response to immunogenic chemotherapy by promoting dendritic cell maturation.

Autor: Lin YS; Department of Pathology, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan, ROC., Chiang SF; Lab of Precision Medicine, Feng-Yuan Hospital, Ministry of Health and Welfare, Taichung, 42055, Taiwan, ROC., Chen CY; Proton Therapy and Science Center, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan, ROC., Hong WZ; Proton Therapy and Science Center, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan, ROC., Chen TW; Graduate Institute of Biomedical Science, China Medical University, Taichung, 40402, Taiwan, ROC.; Department of Pathology, Asia University Hospital, Asia University, Taichung, 41354, Taiwan, ROC., Chen WT; Department of Colorectal Surgery, China Medical University HsinChu Hospital, China Medical University, HsinChu, 302, Taiwan, ROC.; Department of Colorectal Surgery, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan, ROC.; Department of Surgery, School of Medicine, China Medical University, Taichung, 40402, Taiwan, ROC., Ke TW; Department of Colorectal Surgery, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan, ROC.; School of Chinese Medicine, China Medical University, Taichung, 40402, Taiwan, ROC., Yang PC; Proton Therapy and Science Center, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan, ROC., Liang JA; Department of Radiation Oncology, China Medical University Hospital, China Medical University, Taichung, Taiwan, ROC.; Department of Radiotherapy, School of Medicine, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan, ROC., Shiau AC; Proton Therapy and Science Center, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan, ROC.; Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, 40402, Taiwan, ROC., Chao KSC; Proton Therapy and Science Center, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan, ROC. d94032@mail.cmuh.org.tw.; Graduate Institute of Biomedical Science, China Medical University, Taichung, 40402, Taiwan, ROC. d94032@mail.cmuh.org.tw.; Department of Radiation Oncology, China Medical University Hospital, China Medical University, Taichung, Taiwan, ROC. d94032@mail.cmuh.org.tw.; Department of Radiotherapy, School of Medicine, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan, ROC. d94032@mail.cmuh.org.tw., Huang KC; Department of Biomedical Imaging and Radiological Science, China Medical University, Taichung, 40402, Taiwan, ROC. chihyang0425@mail.cmu.edu.tw.; Translation Research Core, China Medical University Hospital, China Medical University, Taichung, 40402, Taiwan, ROC. chihyang0425@mail.cmu.edu.tw.
Jazyk: angličtina
Zdroj: Cancer immunology, immunotherapy : CII [Cancer Immunol Immunother] 2023 Jul; Vol. 72 (7), pp. 2283-2297. Date of Electronic Publication: 2023 Mar 07.
DOI: 10.1007/s00262-023-03416-4
Abstrakt: The CD39-CD73-adenosinergic pathway converts adenosine triphosphate (ATP) to adenosine for inhibiting anti-tumor immune responses. Therefore, targeting CD73 to reinvigorate anti-tumor immunity is considered the novel cancer immunotherapy to eradicate tumor cells. To fully understand the critical role of CD39/CD73 in colon adenocarcinoma (COAD), this study aims to comprehensive investigate the prognostic significance of CD39 and CD73 in stage I-IV COAD. Our data demonstrated that CD73 staining strongly marked malignant epithelial cells and CD39 was highly expressed in stromal cells. Attractively, tumor CD73 expression was significantly associated with tumor stage and the risk of distant metastasis, which suggested CD73 was as an independent factor for colon adenocarcinoma patients in univariate COX analysis [HR = 1.465, 95%CI = 1.084-1.978, p = 0.013]; however, high stromal CD39 in COAD patients was more likely to have favorable survival outcome [HR = 1.458, p = 1.103-1.927, p = 0.008]. Notably, high CD73 expression in COAD patients showed poor response to adjuvant chemotherapy and high risk of distant metastasis. High CD73 expression was inversely associated with less infiltration of CD45 + and CD8 + immune cells. However, administration with anti-CD73 antibodies significantly increased the response to oxaliplatin (OXP). Blockade of CD73 signaling synergistically enhanced OXP-induced ATP release, which is a marker of immunogenic cell death (ICD), promotes dendritic cell maturation and immune cell infiltration. Moreover, the risk of colorectal cancer lung metastasis was also decreased. Taken together, the present study revealed tumor CD73 expression inhibited the recruitment of immune cells and correlated with a poor prognosis in COAD patients, especially patients received adjuvant chemotherapy. Targeting CD73 to markedly increased the therapeutic response to chemotherapy and inhibited lung metastasis. Therefore, tumor CD73 may be an independent prognostic factor as well as the potential of therapeutic target for immunotherapy to benefit colon adenocarcinoma patients.
(© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.)
Databáze: MEDLINE
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