Targeting CD47 for cancer immunotherapy

Jiang, Zhongxing; Sun, Hao; Yu, Jifeng; Tian, Wenzhi; Song, Yongping

doi:10.1186/s13045-021-01197-w

Cited by 171 publications

(154 citation statements)

References 83 publications

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“…Although macrophages, granulocytes, dendritic cells, and monocytes can all express SIPRα, it is predominantly expressed on macrophages in tumors [ 49 ]. Furthermore, the function of the CD47/SIRPα axis was established in the late 2000s and has been termed the first tumor phagocytosis-related checkpoint (also known as the macrophage “don’t eat me” signal) [ 50 ].…”

Section: Discussionmentioning

confidence: 99%

SIRPα and PD1 expression on tumor-associated macrophage predict prognosis of intrahepatic cholangiocarcinoma

Yang

Yan

et al. 2022

J Transl Med

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Background The phagocytosis checkpoints of CD47/SIRPα, PD1/PDL1, CD24/SIGLEC10, and MHC/LILRB1 have shown inhibited phagocytosis of macrophages in distinct tumors. However, phagocytosis checkpoints and their therapeutic significance remain largely unknown in intrahepatic cholangiocarcinoma (ICC) patients. Methods We analyzed sequencing data from the Cancer Genome Atlas (TCGA) and identified differently expressed genes between tumors and para‐tumors. Then, we investigated the expression of CD68, SIRPα, PD1, and SIGLEC10 by IHC in 81 ICC patients, and the clinical significance of these markers with different risk factors was also measured. Results Tumor infiltration immune cells analysis from the TCGA data revealed that macrophages significantly increased. Further analysis showed that M0 macrophages were significantly higher and M2 macrophages were significantly lower in ICC compared with paracancerous tissues, while there was no significant difference in M1 macrophages. We then examined some of M1 and M2 markers, and we found that M1 markers (iNOS, TNF, IL12A, and B) increased, while M2 markers (ARG1 and CD206) decreased in ICCs compared with paracancerous tissues. Furthermore, the expression of CD68, SIRPα, PD1, and SIGLEC10 increased significantly, but LILRB1 expression did not. We also examined the expression of CD68, SIRPα, PD1, and SIGLEC10 in 81 ICC patients by IHC, which revealed a similar expression pattern to that which emerged from the TCGA data. Upon analyzing the correlation between these markers and the progression of ICC patients, we found that the high expression of CD68, SIRPα, and PD1 are correlated with poor progression among ICC patients, while SIGLEC10 shows no correlation. More SIRPα+ or PD1+ TAMs were observed in the tumor tissues of ICC patients with HBV infections compared to non‐HBV‐infected patients. Multivariate analysis indicated that SIRPα and PD1 expression are independent indicators of ICC patient prognosis. Conclusion Hyperactivated CD47/SIRPα and PD1/PD‐L1 signals in CD68+ TAMs in tumor tissues are negative prognostic markers for ICCs after resection. Furthermore, anti-CD47 in combination with anti-PD1 or CD47/PD1 bispecific antibody (BsAb) may represent promising treatments for ICC. Further studies are also required in the future to confirmed our findings.

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Section: Discussionmentioning

confidence: 99%

SIRPα and PD1 expression on tumor-associated macrophage predict prognosis of intrahepatic cholangiocarcinoma

Yang

Yan

et al. 2022

J Transl Med

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“…DC/PD-1 immunotherapy combinations are currently under preclinical and clinical investigation in recurrent advanced brain tumors, advanced and relapsed NSCLC, MM and advanced renal cell carcinoma [ 151 ]. Additionally, various other combination therapies that exploit alternative immune targets and other therapeutic modalities have been explored for cancer treatment [ 152 – 154 ], especially with the development of a new generation of immune checkpoint inhibitors and other inhibitory targets [ 155 – 161 ]. The combination of a DC/AML cell fusion vaccine and checkpoint blocking therapy provides unique synergy to induce durable activation of leukemia specific immunity, protect against lethal tumor challenges, and selectively amplify tumor-reactive clones [ 162 ].…”

Section: Enhancing DC Vaccine Efficacy Via Coadministration With Chemotherapy and Checkpoint Inhibitorsmentioning

confidence: 99%

Research progress on dendritic cell vaccines in cancer immunotherapy

Sun

Cao

et al. 2022

Exp Hematol Oncol

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Dendritic cell (DC) vaccines induce specific immune responses that can selectively eliminate target cells. In recent years, many studies have been conducted to explore DC vaccination in the treatment of hematological malignancies, including acute myeloid leukemia and myelodysplastic syndromes, as well as other nonleukemia malignancies. There are at least two different strategies that use DCs to promote antitumor immunity: in situ vaccination and canonical vaccination. Monocyte-derived DCs (mo-DCs) and leukemia-derived DCs (DCleu) are the main types of DCs used in vaccines for AML and MDS thus far. Different cancer-related molecules such as peptides, recombinant proteins, apoptotic leukemic cells, whole tumor cells or lysates and DCs/DCleu containing a vaster antigenic repertoire with RNA electroporation, have been used as antigen sources to load DCs. To enhance DC vaccine efficacy, new strategies, such as combination with conventional chemotherapy, monospecific/bispecific antibodies and immune checkpoint-targeting therapies, have been explored. After a decade of trials and tribulations, much progress has been made and much promise has emerged in the field. In this review we summarize the recent advances in DC vaccine immunotherapy for AML/MDS as well as other nonleukemia malignancies.

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“…CD47 is expressed on all normal cells and functions as a safety mechanism to prevent phagocytosis. However, CD47 is frequently upregulated on cancer cells compared to normal cells and thus is regarded as an attractive target for cancer immunotherapy [ 153 ]. Inhibiting CD47 hinders cancer immune escape and increases phagocytic activity.…”

Section: Therapeutic Options For Targeting Tamsmentioning

confidence: 99%

Tumor-Associated Macrophages in Gliomas—Basic Insights and Treatment Opportunities

Andersen

Miletić

Hossain

2022

Cancers

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Glioma refers to a group of primary brain tumors which includes glioblastoma (GBM), astrocytoma and oligodendroglioma as major entities. Among these, GBM is the most frequent and most malignant one. The highly infiltrative nature of gliomas, and their intrinsic intra- and intertumoral heterogeneity, pose challenges towards developing effective treatments. The glioma microenvironment, in addition, is also thought to play a critical role during tumor development and treatment course. Unlike most other solid tumors, the glioma microenvironment is dominated by macrophages and microglia—collectively known as tumor-associated macrophages (TAMs). TAMs, like their homeostatic counterparts, are plastic in nature and can polarize to either pro-inflammatory or immunosuppressive states. Many lines of evidence suggest that immunosuppressive TAMs dominate the glioma microenvironment, which fosters tumor development, contributes to tumor aggressiveness and recurrence and, very importantly, impedes the therapeutic effect of various treatment regimens. However, through the development of new therapeutic strategies, TAMs can potentially be shifted towards a proinflammatory state which is of great therapeutic interest. In this review, we will discuss various aspects of TAMs in the context of glioma. The focus will be on the basic biology of TAMs in the central nervous system (CNS), potential biomarkers, critical evaluation of model systems for studying TAMs and finally, special attention will be given to the potential targeted therapeutic options that involve the TAM compartment in gliomas.

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Targeting CD47 for cancer immunotherapy

Cited by 171 publications

References 83 publications

SIRPα and PD1 expression on tumor-associated macrophage predict prognosis of intrahepatic cholangiocarcinoma

SIRPα and PD1 expression on tumor-associated macrophage predict prognosis of intrahepatic cholangiocarcinoma

Research progress on dendritic cell vaccines in cancer immunotherapy

Tumor-Associated Macrophages in Gliomas—Basic Insights and Treatment Opportunities

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