Immunostimulant Hydrogel-Guided Tumor Microenvironment Reprogramming to Efficiently Potentiate Macrophage-Mediated Cellular Phagocytosis for Systemic Cancer Immunotherapy.

Macrophage-mediated cellular phagocytosis (MMCP) plays a critical role in conducting antitumor immunotherapy but is usually impaired by the intrinsic phagocytosis evading ability of tumor cells and the immunosuppressive tumor microenvironment (TME). Herein, a MMCP-boosting hydrogel (TCCaGM) was elaborately engineered by encapsulating granulocyte-macrophage colony-stimulating factor (GM-CSF) and a therapeutic nanoplatform (TCCaN) that preloaded with the tunicamycin (Tuni) and catalase (CAT) with the assistance of CaCO3 nanoparticles (NPs). Strikingly, the hypoxic/acidic TME was efficiently alleviated by the engineered hydrogel, "eat me" signal calreticulin (CRT) was upregulated, while the "don't eat me" signal CD47 was downregulated on tumor cells, and the infiltrated DCs were recruited and activated, all of which contributed to boosting the macrophage-mediated phagocytosis and initiating tumor-specific CD8+ T cells responses. Meanwhile, the remodeled TME was beneficial to accelerate the polarization of tumor-associated macrophages (TAMs) to the antitumoral M1-like phenotype, further heightening tumoricidal immunity. With the combination of PD-1 antibody (αPD-1), the designed hydrogel significantly heightened systemic antitumor immune responses and long-term immunological effects to control the development of primary and distant tumors as well as suppress tumor metastasis and recurrence, which established an optimal strategy for high-performance antitumor immunotherapy.

Correlation between single nucleotide polymorphisms of tumor suppressor gene PTEN and nasopha-ryngeal carcinoma / 新乡医学院学报

Objective To investigate the relationship between single nucleotide polymorphisms of tumor suppressor gene PTEN and nasopharyngeal carcinoma in Jiamusi Han population. Methods The blood samples of 132 patients with naso-pharyngeal carcinoma(nasopharyngeal carcinoma group)and 73 healthy people(control group)were selected from September 2008 to January 2018 in the First Affiliated Hospital of Jiamusi University. The whole genome DNA was extracted,and the pol-ymorphisms of rs532678 and rs701848 were detected by restriction fragment length polymorphism analysis. The relationship be-tween the polymorphism of PTEN gene and nasopharyngeal carcinoma was analyzed. Results The genotype and allele frequen-cy distributions of rs532678 and rs701848 loci were in line with the Hardy-Weinberg genetic balance law in the two groups (P > 0. 05). The genotypic frequency of CC,CT and TT at the rs532678 locus of PTEN gene in the control group was 0. 630, 0. 342 and 0. 027 respectively;and the allele frequency of C and T was 0. 801 and 0. 198 respectively. The genotypic frequency of CC,CT and TT at the rs532678 locus of PTEN gene in the nasopharyngeal carcinoma group was 0. 716,0. 265 and 0. 015 re-spectively;and the allele frequency of C and T was 0. 852 and 0. 147 respectively. There was no significant difference in geno-type distribution and allele frequency distribution at the rs532678 locus of PTEN gene between the two groups(P > 0. 05). The genotypic frequency of CC,CT and TT at the rs701848 locus of the PTEN gene in the control group was 0. 657,0. 342 and 0. 000 respectively;and the allele frequency of C and T was 0. 828 and 0. 171 respectively. The genotypic frequency of CC,CT and TT at the rs701848 locus of PTEN gene in the nasopharyngeal carcinoma group was 0. 424,0. 500 and 0. 075 respectively;and the allele frequency of C and T was 0. 674 and 0. 325 respectively. The frequencies of CT,TT genotype and T allele of rs701848 locus in the nasopharyngeal carcinoma group were significantly higher than those in the control group(P < 0. 05). The frequencies of CC genotype and C allele in the nasopharyngeal carcinoma group were significantly lower than those in the control group(P < 0. 05). The individual with CT + TT genotype at the rs701848 locus of PTEN gene had higher risk for naso-pharyngeal carcinoma(P < 0. 05,OR = 2. 606,95％ confidence interval:1. 439 - 4. 720). The risk for nasopharyngeal carcino-ma in the individual with CT + TT genotype was 2. 606 times as much as the individual carrying CC genotype. Conclusion The rs532678 polymorphism of PTEN gene is not associated with the susceptibility to nasopharyngeal carcinoma. The polymor-phism of rs701848 locus is associated with the susceptibility to nasopharyngeal carcinoma. The individual carrying CT + TT genotype has higher risk for nasopharyngeal carcinoma.