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Annexin A5 as an immune checkpoint inhibitor and tumor-homing molecule for cancer treatment.

ABSTRACT: The interaction between immune cells and phosphatidylserine (PS) molecules exposed on the surface of apoptotic-tumor bodies, such as those induced by chemotherapies, contributes to the formation of an immunosuppressive tumor microenvironment (TME). Annexin A5 (AnxA5) binds with high affinity to PS externalized by apoptotic cells, thereby hindering their interaction with immune cells. Here, we show that AnxA5 administration rescue the immunosuppressive state of the TME induced by chemotherapy. Due to the preferential homing of AnxA5 to the TME enriched with PS+ tumor cells, we demonstrate in vivo that fusing tumor-antigen peptide to AnxA5 significantly enhances its immunogenicity and antitumor efficacy when administered after chemotherapy. Also, the therapeutic antitumor effect of an AnxA5-peptide fusion can be further enhanced by administration of other immune checkpoint inhibitors. Our findings support the administration of AnxA5 following chemotherapy as a promising immune checkpoint inhibitor for cancer treatment.

SUBMITTER: Kang TH

PROVIDER: S-EPMC7048819 | biostudies-literature | 2020 Feb

REPOSITORIES: biostudies-literature

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Annexin A5 as an immune checkpoint inhibitor and tumor-homing molecule for cancer treatment.

Kang Tae Heung TH Park Jung Hwa JH Yang Andrew A Park Hyun Jin HJ Lee Sung Eun SE Kim Young Seob YS Jang Gun-Young GY Farmer Emily E Lam Brandon B Park Yeong-Min YM Hung Chien-Fu CF

Nature communications 20200228 1

The interaction between immune cells and phosphatidylserine (PS) molecules exposed on the surface of apoptotic-tumor bodies, such as those induced by chemotherapies, contributes to the formation of an immunosuppressive tumor microenvironment (TME). Annexin A5 (AnxA5) binds with high affinity to PS externalized by apoptotic cells, thereby hindering their interaction with immune cells. Here, we show that AnxA5 administration rescue the immunosuppressive state of the TME induced by chemotherapy. Du ...[more]

PMID: 32111835

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Project description:Annexin A5 (ANXA5), which is known as a protein with anticoagulative function, may play a role in triglyceride biosynthesis. Triglycerides are involved in lipid and energy metabolism, which are important in the elucidation of obesity. To investigate the association between single-nucleotide polymorphisms (SNPs) of ANXA5 and obesity in a Korean population, 372 participants (213 overweight/obese individuals and 159 control subjects) were enrolled from the Kyung Hee University Medical Center and Keimyung University Dongsan Medical Center. The genotypes of five SNPs (rs12510548, rs4240260, rs3756281, rs13136094 and rs6534313) were evaluated in ANXA5 using the multiple logistic regression analysis with the codominant 1, codominant 2, dominant, recessive and log-additive models. The genotype and allele frequencies of the five investigated SNPs exhibited significant differences between the control and the overweight/obese groups: rs12510548 (P=0.004 in the codominant 2 model, P=0.0019 in the recessive model, P=0.027 in the log-additive model and P=0.026 in allele frequencies); rs4240260 (P=0.002 and Fisher's exact P=0.0006 in the codominant 2 model, P=0.0007 and Fisher's exact P=0.0007 in the recessive model, P=0.020 and Fisher's exact P=0.0019 in the log-additive model and P=0.020 in allele frequencies); rs3756281 (P=0.016 in the codominant 2 model and P=0.0094 in the recessive model); rs13136094 (P=0.0030 and Fisher's exact P=0.0011 in the codominant 2 model, P=0.0012 and Fisher's exact P=0.0013 in the recessive model, P=0.034 and Fisher's exact P=0.0035 in the log-additive model and P=0.024 in allele frequencies); and rs6534313 (P=0.0010 and Fisher's exact P=0.0003 in the codominant 2 model, P=0.0003 and Fisher's exact P=0.0003 in the recessive model, P=0.0075 and Fisher's exact P=0.0010 in the log-additive model and P=0.005 in allele frequencies). Two haplotypes were weakly associated with obesity (GGATG, P=0.037 and CAGCC, P=0.020). Results of the present study suggested that ANXA5 may be associated with the development of obesity in a Korean population.

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Annexin A5 as an immune checkpoint inhibitor and tumor-homing molecule for cancer treatment.

Publications

Annexin A5 as an immune checkpoint inhibitor and tumor-homing molecule for cancer treatment.

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