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Frontiers of Medicine

ISSN 2095-0217

ISSN 2095-0225(Online)

CN 11-5983/R

Postal Subscription Code 80-967

2018 Impact Factor: 1.847

Front. Med.    2018, Vol. 12 Issue (4) : 473-480
Activation of phagocytosis by immune checkpoint blockade
Chia-Wei Li1, Yun-Ju Lai2, Jennifer L. Hsu1, Mien-Chie Hung1()
1. Department of Molecular and Cellular Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
2. Department of Neurology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, TX 77030, USA
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Inhibition of macrophage-mediated phagocytosis has emerged as an essential mechanism for tumor immune evasion. One mechanism inhibiting the innate response is the presence of the macrophage inhibitory molecule, signal regulatory protein-α (SIRPα), on tumor-associated macrophages (TAMs) and its cognate ligand cluster of differentiation 47 (CD47) on tumor cells in the tumor microenvironment. On the basis of a recently discovered programmed death protein 1 (PD-1) in TAMs, we discuss the potential inhibitory receptors that possess new functions beyond T cell exhaustion in this review. As more and more immune receptors are found to be expressed on TAMs, the corresponding therapies may also stimulate macrophages for phagocytosis and thereby provide extra anti-tumor benefits in cancer therapy. Therefore, identification of biomarkers and combinatorial therapeutic strategies, have the potential to improve the efficacy and safety profiles of current immunotherapies.

Keywords CD47      PD-1      PD-L1      immunotherapy      TAM      phagocytosis      macrophage     
Corresponding Authors: Mien-Chie Hung   
Just Accepted Date: 09 July 2018   Issue Date: 03 September 2018
 Cite this article:   
Chia-Wei Li,Yun-Ju Lai,Jennifer L. Hsu, et al. Activation of phagocytosis by immune checkpoint blockade[J]. Front. Med., 2018, 12(4): 473-480.
Fig.1  Anti-PD-1 therapy induces both TAMs and CD8+ T cell activity. (A) The expression of PD-1 on the tumor-associated macrophages (TAMs) and T cell inhibits antitumor immunity. (B) PD-1 antibody induces innate immunity by TAM phagocytosis and adaptive immunity by T cell cytolytic activity.
Group Macrophages T cells Tumors Suppressive/stimulatory Localization Targeted drug References
1 PD-1 (CD279) PD-L1 Suppressive TAMs Available [17]
PD-1 PD-L1 Suppressive [42]
PD-L1 (B7-H1; CD274)
PD-L2 (CD273)
PD-L1 PD-1 Suppressive TAMs [44]
RGMb PD-L2 Suppressive TAMs [45]
2 B7-H4 TAMs Available [46]
B7-H4 Stimulatory [47]
3 TIM3 GAL9 Suppressive TAMs Available [48]
TIM3 GAL9 Suppressive [49]
4 PVR (CD155) TIGIT Suppressive Available [50]
TIGIT PVR Suppressive [51]
CD226 PVR Stimulatory [52]
PVR (CD155) CD226 Stimulatory [53]
CD112R CD112 Suppressive [54]
5 B7-1 (CD80), B7-2 (CD86) Available [55]
CD28 B7-1, B7-2 Stimulatory [56]
CTLA-4 B7-1, B7-2 Suppressive
6 SIRPa CD47 Suppressive TAMs Available [57]
7 4-1BBL (CD137L) 4-1BB (CD137) 4-1BBL Stimulatory TAMs Available [58]
8 LILRB1 MHC I Suppressive TAMs N/A [19]
9 LRP1 CRT Stimulatory TAMs N/A [59]
10 RAGE S100 Suppressive TAMs N/A [60]
11 CD40 CD40L Stimulatory TAMs N/A [61]
CD40 CD40L [62]
12 OX40L OX40 Stimulatory Available [63]
OX40 OX40L [64]
13 ICOSL ICOS ICOSL Stimulatory TAMs Available [65]
14 VISTA TAMs Available [66,67]
Tab.1  Immune checkpoints expression across three cell types categorized into different receptor-ligand pair groups
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