Targeting CD39 in cancer

Moesta, Achim K.; Li, Xian-Yang; Smyth, Mark J.

doi:10.1038/s41577-020-0376-4

Cited by 231 publications

(216 citation statements)

References 142 publications

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“…However, with the in-depth study of various cells in TME, more and more evidence shows that CD39 plays multiple biological functions on the surface of different cells. 9 The expression of CD39 was also detected on T cells, especially on CD8 +T cells with hallmarks of chronic antigenic stimulation at the tumor site and was associated with clinical beneficial factors in multiple cancers. 15,26 An earlier study reported that CD39 is a marker for CD8+ T cells to mediate specific killer function.…”

Section: Dovepressmentioning

confidence: 99%

“…Since the discovery and characterization of PD-1, kinds of ICs have been investigated including T-cell membrane protein 3 (TIM-3, encoded by HAVCR2), 6 lymphocyte activation gene 3 (LAG-3), 6 costimulatory molecule CD134 (OX40, encoded by TNFRSF4), 7 cluster of differentiation 137 (CD137 (4-1BB), encoded by TNFRSF9), 8 ectoenzyme CD39 (encoded by ENTPD1), 9 and so on. Although these biomarkers have been studied deeply in other cancers and corresponding clinical trials have been carried out, there are few studies in BLCA.…”

Section: Introductionmentioning

confidence: 99%

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CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer

Zhu

Zhao

Feng

et al. 2021

OTT

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Introduction: Although immunotherapy works well in parts of patients with bladder cancer (BLCA), its overall response rate of anti-PD-1 inhibitors remains unsatisfactory. Besides, growing evidence shows that tumor-infiltrating lymphocytes (TILs) immunotherapy has demonstrated excellent efficacy in various cancers. Considering the huge heterogeneity and low overall survival rate of BLCA, it is urgent to explore the new immune checkpoints (ICs) or TILs therapy to improve the survival prognosis for BLCA patients. Materials and Methods: The public bioinformatics databases were used to explore the prognostic value of 5 potential ICs targets (TIM-3, LAG-3, OX40, 4-1BB and CD39). A total of 46 BLCA patients undergoing surgical treatment at our hospital from May 2020 to October 2020 were enrolled in this study. The expressions of PD-1, TIM-3, LAG-3, OX40, 4-1BB, and CD39 in T cells of BLCA patients were explored by flow cytometry, and the correlation between different subgroups of T cells and clinicopathological parameters was analyzed. Besides, the mouse CD4+CD39+ T cells, CD4+CD39-T cells, CD8+CD39+ T cells, and CD8+CD39-T cells were sorted and co-cultured with MB49 bladder cancer cell lines in vitro to investigate the potential biomarker of tumor-reactive TILs. Results: Public bioinformatics databases analyses show that only the high expression of CD39 was significantly associated with advanced tumor stage (P < 0.001) and tend to result in a worse survival rate. In our study, the elevated expression of CD39 in CD4+/CD8+ T cells were significantly associated with the pathological T stage (pT <2, P = 0.041) and papillary tumor (P = 0.038). Moreover, the CD8+CD39+ T cells showed a stronger tumorkilling effect and produced a higher level of IFN-γ than other T cell populations. Conclusion: CD39 may be a potential prognostic marker in BLCA, and CD8+CD39+ T cells may be selected as tumor-reactive and killing T cells for TILs therapy.

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Section: Dovepressmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer

Zhu

Zhao

Feng

et al. 2021

OTT

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“…This antibody increased antitumor activity when administrated with chemotherapeutic drugs, such as oxiplatin (Perrot et al, 2019). Other antibodies including anti-CD39, TTX-030, and SRF617 have been tested in phase one clinical trials, both as single agents and in combination with chemotherapy, with the aim of improving the antitumoral response (Moesta et al, 2020).…”

Section: Cd39/cd73 Axis As Pharmacological Target For Immunotherapymentioning

confidence: 99%

CD39 and CD73 as Promising Therapeutic Targets: What Could Be the Limitations?

et al. 2021

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“…Furthermore, they produce less IFN-γ and do not proliferate. Instead, their expression of the ATPase CD39 might rather point to an immune suppressive function [90,91]. Furthermore, at least in Burkitt's lymphoma patients, CD56 − CD16 + NK cells seem to retain MIP1β/CCL4 production, which can attract CCR5 + regulatory T and suppressive myeloid cell populations [92,93].…”

Section: Modulation Of Nk Cell Responses By Kshvmentioning

confidence: 99%

Natural Killer Cell Responses during Human γ-Herpesvirus Infections

Münz

2021

Vaccines

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Herpesviruses are main sculptors of natural killer (NK) cell repertoires. While the β-herpesvirus human cytomegalovirus (CMV) drives the accumulation of adaptive NKG2C-positive NK cells, the human γ-herpesvirus Epstein–Barr virus (EBV) expands early differentiated NKG2A-positive NK cells. While adaptive NK cells support adaptive immunity by antibody-dependent cellular cytotoxicity, NKG2A-positive NK cells seem to preferentially target lytic EBV replicating B cells. The importance of this restriction of EBV replication during γ-herpesvirus pathogenesis will be discussed. Furthermore, the modification of EBV-driven NK cell expansion by coinfections, including by the other human γ-herpesvirus Kaposi sarcoma-associated herpesvirus (KSHV), will be summarized.

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Targeting CD39 in cancer

Cited by 231 publications

References 142 publications

CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer

CD8+CD39+ T Cells Mediate Anti-Tumor Cytotoxicity in Bladder Cancer

CD39 and CD73 as Promising Therapeutic Targets: What Could Be the Limitations?

Natural Killer Cell Responses during Human γ-Herpesvirus Infections

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