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Abrogation of Hn RNP L enhances anti-pd-1 therapy efficacy via diminishing pd-L1 and promoting CD8^(+) T cell-mediated ferroptosis in castration-resistant prostate cancer

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Acta Pharmaceutica Sinica B 2022年第2期12卷 692-707页

作者： Xumin Zhou Libin Zou Hangyu Liao Junqi Luo Taowei Yang Jun Wu Wenbin Chen Kaihui Wu Shengren Cen Daojun Lv Fangpeng Shu Yu Yang Chun Li Bingkun Li Xiangming Mao Department of Urology Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China Second Department of Hepatobiliary Surgery Zhujiang HospitalSouthern Medical UniversityGuangzhou 510280China Nursing Department Nanfang HospitalSouthern Medical UniversityGuangzhou 510515China Department of Urology Minimally Invasive Surgery Centerthe First Affiliated Hospital of Guangzhou Medical UniversityGuangzhou 510120China Department of Urology Guangzhou Women and Children’s Medical CenterGuangzhou Medical UniversityGuangzhou 510623China Department of Urology Peking University Shenzhen HospitalShenzhen 518036China

Owing to incurable castration-resistant prostate cancer(CRPC)ultimately developing after treating with androgen deprivation therapy(ADT),it is vital to devise new therapeutic strategies to treat *** that target programmed cell death protein 1(pd-1)and programmed death ligand-1(pd-L1)have been approved for human cancers with clinical ***,many patients,especially prostate cancer,fail to respond to anti-pd-1/pd-L1 treatment,so it is an urgent need to seek a support strategy for improving the traditional pd-1/pd-L1 targeting *** the present study,analyzing the data from our prostate cancer tissue microarray,we found that pd-L1 expression was positively correlated with the expression of heterogeneous nuclear ribonucleoprotein L(Hn RNP L).Hence,we further investigated the potential role of Hn RNP L on the pd-L1 expression,the sensitivity of cancer cells to T-cell killing and the synergistic effect with anti-pd-1 therapy in ***,Hn RNP L knockdown effectively decreased pd-L1 expression and recovered the sensitivity of cancer cells to T-cell killing in vitro and in vivo,on the contrary,Hn RNP L overexpression led to the opposite effect in CRPC *** addition,consistent with the previous study,we revealed that ferroptosis played a critical role in T-cell-induced cancer cell death,and Hn RNP L promoted the cancer immune escape partly through targeting YY1/pd-L1 axis and inhibiting ferroptosis in CRPC ***,Hn RNP L knockdown enhanced antitumor immunity by recruiting infiltrating CD8^(+)T cells and synergized with anti-pd-1 therapy in CRPC *** study provided biological evidence that Hn RNP L knockdown might be a novel therapeutic agent in pd-L1/pd-1 blockade strategy that enhanced anti-tumor immune response in CRPC.

关键词： HnRNP L pd-L1 YY1 Ferroptosis Immune escape Immune checkpoint blockade anti-pd-1 therapy Castration-resistant prostate cancer

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Plasma D-dimer and IL-6 associated with treatment response and progress free survival in advanced non-small cell lung cancer patients treated with anti-pd-1 therapy

Plasma D-dimer and IL-6 associated with treatment response a...

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2021年中国肿瘤标志物学术大会暨第十五届肿瘤标志物青年科学家论坛

作者： Chong Chen Li Ren Tianjin Medical University Cancer Institute and Hospital

Background: The treatment response of immune checkpoint inhibitors(ICIs) remains unexpected and there is significant individual variability in the efficacy of different patients with advanced non-small cell lung cancer. This study aims to find peripheral blood biomarkers predicting the efficacy and PFS(progression-free survival) of anti-programmed death-1(anti-pd-1) treatment in patients with advanced non-small cell lung cancer(NSCLC), which can be used to guide the adjustment of anti-pd-1 treatment regimens to bring greater clinical benefit to NSCLC ***: A systematic review of 103 patients with advanced or recurrent NSCLC who received anti-pd-1 therapy(pembrolizumab or carrelixumab) inpatiently at Tianjin Medical University Cancer Hospital between January 2018 and April 2021. The cut-off values for carcinoembryonic antigen(CEA),cytokeratin19 fragment 21-1(CYFR21-1), squamous cell carcinoma(SCC), tissue polypeptidespecific antigens(TPSA), D-dimer and serum inflammatory markers were determined by receiver operating characteristic curve analysis. Tumor response was assessed by computed tomography according to the Response Evaluation Criteria in Solid Tumors, version ***: Peripheral blood biomarkers IL-6 and D-dimer can predict the clinical value of treatment effect at6-8 weeks of anti-pd-1 treatment, with AUC areas corresponding to 0.765 and 0.804. Analyses of survival showed that IL-6 ≥ 8.03 pg/mL and DD≥ 917.2 ng/mL were independent predictors of progression-free survival(PFS). A PFS prediction model for anti-pd-1 treatment of NSCLC using the new cut-off values: using "IL-6 ≥ 8.03 pg/mL" or "DD ≥ 917.20 ng/mL" as a score of "1". The results showed that the higher the score of combined IL-6 and D-dimer, the shorter the PFS ***: High expression of IL-6 in patients with advanced NSCLC predicts poor efficacy and short duration of PFS with anti-pd-1 therapy;Increasing the cut-off value of D-dimer to 917.20 ng/mL predicts the occurrence o

关键词： D-dimer IL-6 advanced non-small cell lung cancer anti-pd-1 therapy

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