PMID- 36268178
OWN - NLM
STAT- MEDLINE
DCOM- 20221024
LR  - 20221104
IS  - 2162-402X (Electronic)
IS  - 2162-4011 (Print)
IS  - 2162-4011 (Linking)
VI  - 11
IP  - 1
DP  - 2022
TI  - Targeting depletion of myeloid-derived suppressor cells potentiates PD-L1 
      blockade efficacy in gastric and colon cancers.
PG  - 2131084
LID - 10.1080/2162402X.2022.2131084 [doi]
LID - 2131084
AB  - Myeloid-derived suppressor cells (MDSCs) have been demonstrated to suppress 
      antitumor immunity and induce resistance to PD-1/PD-L1 blockade immunotherapy in 
      gastric and colon cancer patients. Herein, we found that MDSCs accumulate in mice 
      bearing syngeneic gastric cancer and colon cancer. Death receptor 5 (DR5), a 
      receptor of TNF-related apoptosis-inducing ligand (TRAIL), was highly expressed 
      on MDSCs and cancer cells; targeting DR5 using agonistic anti-DR5 antibody 
      (MD5-1) specifically depleted MDSCs and induced enrichment of CD8(+) T 
      lymphocytes in tumors and exhibited stronger tumor inhibition efficacy in 
      immune-competent mice than in T-cell-deficient nude mice. Importantly, the 
      combination of MD5-1 and anti-PD-L1 antibody showed synergistic antitumor effects 
      in gastric and colon tumor-bearing mice, resulting in significantly suppressed 
      tumor growth and extended mice survival, whereas single-agent treatment had 
      limited effect. Moreover, the combination therapy induced sustained memory 
      immunity in mice that exhibited complete tumor regression. The enhanced antitumor 
      effect was associated with increased intratumoral CD8(+) T-cell infiltration and 
      activation, and a more vigorous tumor-inhibiting microenvironment. In summary, 
      our findings highlight the therapeutic potential of combining PD-L1 blockade 
      therapy with agonistic anti-DR5 antibody that targets MDSCs in gastric and colon 
      cancers.
CI  - (c) 2022 The Author(s). Published with license by Taylor & Francis Group, LLC.
FAU - Tang, Yao
AU  - Tang Y
AD  - State Key Laboratory of Oncogenesis and Related Genes, Department of Oncology, 
      Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 
      China.
FAU - Zhou, Cong
AU  - Zhou C
AD  - State Key Laboratory of Oncogenesis and Related Genes, Department of Oncology, 
      Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 
      China.
FAU - Li, Qingli
AU  - Li Q
AD  - State Key Laboratory of Oncogenesis and Related Genes, Department of Oncology, 
      Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 
      China.
FAU - Cheng, Xiaojiao
AU  - Cheng X
AD  - State Key Laboratory of Oncogenesis and Related Genes, Department of Oncology, 
      Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 
      China.
FAU - Huang, Tinglei
AU  - Huang T
AD  - State Key Laboratory of Oncogenesis and Related Genes, Department of Oncology, 
      Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 
      China.
FAU - Li, Fuli
AU  - Li F
AD  - State Key Laboratory of Oncogenesis and Related Genes, Department of Oncology, 
      Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 
      China.
FAU - He, Lina
AU  - He L
AD  - State Key Laboratory of Oncogenesis and Related Genes, Department of Oncology, 
      Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 
      China.
FAU - Zhang, Baiweng
AU  - Zhang B
AD  - State Key Laboratory of Oncogenesis and Related Genes, Department of Oncology, 
      Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 
      China.
FAU - Tu, Shuiping
AU  - Tu S
AD  - State Key Laboratory of Oncogenesis and Related Genes, Department of Oncology, 
      Renji Hospital, Shanghai Jiao Tong University, School of Medicine, Shanghai, 
      China.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20221013
PL  - United States
TA  - Oncoimmunology
JT  - Oncoimmunology
JID - 101570526
RN  - 0 (Programmed Cell Death 1 Receptor)
RN  - 0 (TNF-Related Apoptosis-Inducing Ligand)
RN  - 0 (Receptors, TNF-Related Apoptosis-Inducing Ligand)
SB  - IM
MH  - Mice
MH  - Animals
MH  - *Myeloid-Derived Suppressor Cells/pathology
MH  - Programmed Cell Death 1 Receptor
MH  - TNF-Related Apoptosis-Inducing Ligand/pharmacology
MH  - Mice, Nude
MH  - Receptors, TNF-Related Apoptosis-Inducing Ligand
MH  - Tumor Microenvironment
MH  - *Colonic Neoplasms/drug therapy
PMC - PMC9578486
OTO - NOTNLM
OT  - Myeloid-derived suppressor cells
OT  - PD-L1
OT  - colon cancer
OT  - death receptor 5
OT  - gastric cancer
OT  - immunotherapy
COIS- No potential conflict of interest was reported by the author(s).
EDAT- 2022/10/22 06:00
MHDA- 2022/10/25 06:00
PMCR- 2022/10/13
CRDT- 2022/10/21 03:10
PHST- 2022/10/21 03:10 [entrez]
PHST- 2022/10/22 06:00 [pubmed]
PHST- 2022/10/25 06:00 [medline]
PHST- 2022/10/13 00:00 [pmc-release]
AID - 2131084 [pii]
AID - 10.1080/2162402X.2022.2131084 [doi]
PST - epublish
SO  - Oncoimmunology. 2022 Oct 13;11(1):2131084. doi: 10.1080/2162402X.2022.2131084. 
      eCollection 2022.