中国医学科学院

Objective To validate F-box protein 2(FBXO2)as a potential tumor-specific pattern recognition ligand for γδ T cells and to characterize its expression in tumor cells and function in immunotherapy.Methods The expression of FBXO2 in various human solid tumor and hematological tumor cell lines was detected by Western blot and flow cytometry.Immobilized FBXO2 recombinant protein was used to expand Vδ2 and Vδ1 γδ T cells from hu-man peripheral blood mono-nuclear cell(PBMC),followed by comprehensive characterization of cellular purity,ab-solute counts,activation marker expression and cytokine secretion profiles.The inhibitory effect of FBXO2-specific antibody on the in vitro cytotoxicity of Vδ1and Vδ2 γδ T cells was evaluated via antibody blockade experiment.Results FBXO2 was expressed in some human solid and hematological tumor cell lines especially in the gastric cancer line SNU601 and the lymphocyte leukemia line Jurkat.Immobilized FBXO2 significantly promoted the ex-pansion of Vδ1 γδ T cells but failed to stimulate Vδ2 γδ T cells.Vδ1 γδ T cells exerted cytotoxic activity by recog-nizing FBXO2 protein while FBXO2 antibody blocked their cytotoxic effects on SNU601 and Jurkat cells with a dose-dependent manner in vitro.Conclusions F-Box2 protein,ectopically expressed on a variety of tumor cell sur-face,may promote the expansion of Vδ1 γδ T cells and enhance the cytotoxicity of γδ T cells against tumor cells in vitro,so this protein molecule is believed to be a tumor-associated protein ligand recognized by γδ T cells.This re-sult suggests a potential nascent target for cancer immunotherapy.

Objective To investigate the awareness levels of human papillomavirus(HPV)and cervical cancer screening,as well as the acceptance of point-of-care testing(POCT)technology among women in Jinan,Shandong province,analyze the influencing factors,and assess their satisfaction with and attitudes toward the promotion of POCT technology.Methods A cross-sectional survey was conducted from May 2024 to June 2025 among 629 women aged 35-64 years who participated in the two-cancer screening program at two community health service centers in Jinan.Information on sociodemographic characteristics,awareness of HPV and cervical cancer screening,and acceptance of POCT technology was collected.Statistical analyses were performed with the chi-square test and binary logistic regression.Results A total of 629 valid questionnaires were obtained.Regarding awareness of HPV and cervical cancer screening,46.26%of participants had heard of HPV,among whom 70.10%knew it as the primary cause of cervical cancer.Overall,80.76%had heard of cervical cancer screening,whereas only 44.09%were aware of specific screening methods.The awareness rates of HPV testing,cytological examination,and visual inspection with acetic acid/Lugol's iodine(VIA/VILI)were 33.86%,24.61%,and 6.99%,respectively.Multivariable analysis showed that compared with women aged 35-44 years,those aged 55-64 years had the lowest awareness level of HPV and cervical cancer screening(OR=0.17,95%CI:0.10-0.31).Compared with women with primary school education or below,those with college education or above had the highest awareness level(OR=3.71,95%CI:1.44-9.56).Regarding acceptance of POCT,55.96%of women expressed willingness to use POCT in future screening.Multivariable analysis indicated that compared with women with primary school education or below,those with senior high school education(OR=0.43,95%CI:0.22-0.81)and those with college or undergraduate education and above(OR=0.37,95%CI:0.17-0.81)showed increased acceptance of POCT.Freelancers(OR=1.93,95%CI:1.08-3.42)and workers(OR=2.33,95%CI:1.10-4.92)showed lower acceptance of POCT technology than unemployed women.In terms of satisfaction and attitudes toward promotion,84.27%of participants believed that POCT could significantly save time and improve the efficiency of conventional screening;83.94%believed that it could significantly improve the accuracy of conventional screening;85.21%reported being very satisfied overall;83.78%held a positive attitude toward its long-term application;and 83.62%were willing to recommend the technology to others.Conclusions Women in Jinan have established basic awareness of HPV and cervical cancer screening,while their understanding of specific screening technologies remains insufficient.Acceptance of POCT technology is at a moderate level,whereas satisfaction with and willingness to promote this technology are relatively high.

Objective To explore the treatment strategy for patients with locally advanced rectal cancer harboring a POLE proofreading deficiency mutation.Methods The clinical data of a patient with locally advanced rectal cancer carrying the POLE p.V411L mutation was analyzed.Results The patient was a 41-year-old male with mismatch re-pair-proficient locally advanced rectal cancer.After initially receiving neoadjuvant concurrent chemoradiotherapy,laparoscopic exploration revealed that the tumor was unresectable.Subsequent genetic testing identified a POLE proofreading deficiency mutation with a tumor mutational burden of 426 mut/MB.The patient then underwent two years of treatment with envafolimab,achieving long-term complete clinical remission.Conclusions Colorectal cancer with POLE proofreading deficiency mutation is highly sensitive to immunotherapy.Genetic testing should be considered to screen for POLE proofreading deficiency mutations and other immunotherapy-sensitive variants in cases where rectal cancer invades surrounding tissues or organs,or when organ function preservation is a concern during surgery.

Objective To investigate the effects of Pifithrin-μ on the proliferation of TSC2 mutant hepatocellular carcinoma cells.Methods The effect of Pifithrin-μ on cell proliferation was evaluated using CCK8 assay in multi-ple lines of Tsc2 mutant mouse embryonic fibroblasts(MEFs)and human hepatocellular carcinoma cells.Lentiviral infection was used to construct hepatocellular carcinoma cells with knockdown or overexpression of TSC2.The pro-tein expression of TSC2 and the downstream effectors of the mTOR pathway were detected by Western blot.Cellular sensitivity to Pifithrin-μ was detected by CCK8.The nude mouse subcutaneous transplantation tumor model was established for evaluation of drug efficacy in vivo.RNA sequencing was used for differential gene and pathway en-richment analysis,which was verified by Western blot and CCK8.Results Pifithrin-μ selectively inhibited the proliferation of Tsc2 mutated MEFs and hepatocellular carcinoma cells in a dose-dependent manner(P＜0.05).Hepatocellular carcinoma cells with TSC2 knockdown showed increased sensitivity to Pifithrin-μ,whereas those with TSC2 overexpression were resistant(P＜0.05).Pifithrin-μ significantly inhibited the growth of Tsc2 mutant transplantation tumors in nude mice(P＜0.05).Pifithrin-μ downregulated the expression of Smad7 protein in Tsc2 mutant cells,resulting in elevated levels of p-Smad2/3 and over-activation of the TGF-β/Smad signaling pathway(P＜0.05).The combination of each of the six cell death inhibitors with Pifithrin-μ revealed that reac-tive oxygen species inhibitor and TGF-β/Smad pathway inhibitor were able to reverse Pifithrin-μ-induced cell death in TSC2 mutant cells(P＜0.05).Conclusions Pifithrin-μ selectively inhibits the proliferation of TSC2 mutant hepatocellular carcinoma cells.This effect is associated with the downregulation of Smad7 and the disrup-tion of the TGF-β/Smad signaling pathway balance.