Zhou, C. *, Y. Hu, E. Arkania, S. Kilickap, K. Ying, F. Xu, L. Wu, X. Wang, M. Viguro, T. Makharadze, H. Sun, F. Luo, J. Shi, A. Zang, Y. Pan, Z. Chen, Z. Jia, V. Kuchava, P. Lu, L. Zhang, Y. Cheng, W. Kang, Q. Wang, H. Yu, J. Li and J. Zhu (2024). "A global phase 3 study of serplulimab plus chemotherapy as first-line treatment for advanced squamous non-small-cell lung cancer (ASTRUM-004)." Cancer Cell 42(2): 198-208.e193.(20240104,上海肺科医院,周彩存)斯鲁利单抗治疗晚期鳞状非小细胞肺癌(sqNSCLC)全球三期临床结果
Du, X.-J., G.-Y. Wang, X.-D. Zhu, Y.-Q. Han, F. Lei, L.-F. Shen, K.-Y. Yang, L. Chen, Y.-P. Mao, L.-L. Tang, L. Li, Z. Wu, G.-Q. Xu, Q. Zhou, J. Huang, R. Guo, Y. Zhang, X. Liu, G.-Q. Zhou, W.-F. Li, C. Xu, L. Lin, Y.-P. Chen, F.-P. Chen, X.-Y. Liang, S.-Y. Chen, S.-Q. Li, C.-Y. Cui, J.-B. Li, J. Ren, M.-Y. Chen*, L.-Z. Liu*, Y. Sun* and J. Ma* (2024). "Refining the 8th edition TNM classification for EBV related nasopharyngeal carcinoma." Cancer Cell 42(3): 464-473.e463.(20240118,中山大学,马骏,孙颖,刘立志,陈明远)基于鼻咽癌临床大数据分析,针对现行国际通用的AJCC/UICC鼻咽癌第八版临床分期系统,首次提出修订建议,有望被新版分期系统采纳,指导未来全球临床治疗。(Cancer Cell | 马骏/孙颖/刘立志/陈明远团队重塑鼻咽癌临床分期标准新模式)
Yang, X., C. Yang, S. Zhang, H. Geng, A. X. Zhu, R. Bernards, W. Qin, J. Fan, C. Wang and Q. Gao (2024). "Precision treatment in advanced hepatocellular carcinoma." Cancer Cell 42(2): 180-197.(20240212,复旦大学,高强,樊嘉;上海交大医学院,王存)全面系统总结了当前晚期肝细胞癌一线治疗方案中生物标志物的最新研究进展,分别讨论了分子分型、微环境异质性和发病病因等对肝细胞癌临床精准治疗的潜在影响,探讨临床前研究成果向临床治疗转化所面临的困境,并对晚期肝癌精准治疗的未来发展趋势提出展望。(Cancer Cell综述 | 樊嘉/高强/覃文新/王存团队探讨晚期肝细胞癌的精准治疗)
Tong, X., A. S. Patel, E. Kim, H. Li, Y. Chen, S. Li, S. Liu, J. Dilly, K. S. Kapner, N. Zhang, Y. Xue, L. Hover, S. Mukhopadhyay, F. Sherman, K. Myndzar, P. Sahu, Y. Gao, F. Li, F. Li, Z. Fang, Y. Jin, J. Gao, M. Shi, S. Sinha, L. Chen, Y. Chen, T. Kheoh, W. Yang, I. Yanai, A. L. Moreira, V. Velcheti, B. G. Neel, L. Hu, J. G. Christensen, P. Olson, D. Gao, M. Q. Zhang, A. J. Aguirre, K.-K. Wong and H. Ji (2024). "Adeno-to-squamous transition drives resistance to KRAS inhibition in LKB1 mutant lung cancer." Cancer Cell 42(3): 413-428.e417.(20240222,中国科学院分子细胞科学卓越创新中心,季红斌;纽约大学,Kwok-Kin Wong;哈佛医学院,Andrew J. Aguirre;清华大学,张奇伟)该研究发现肺腺鳞癌转分化驱动KRAS靶向治疗耐药的产生,在深入解析其分子机制的基础上,鉴定KRT6A可以作为生物学标志物有效预测患者对KRAS靶向治疗的响应。(Cancer Cell | 季红斌/张奇伟等揭示肺腺鳞癌转分化驱动KRAS靶向治疗耐药的产生)
Xiao, S., F. Shi, H. Song, J. Cui, D. Zheng, H. Zhang, K. Tan, J. Wu, X. Chen, J. Wu, Y. Tang, Y. Dai and M. Lu (2024). "Characterization of the generic mutant p53-rescue compounds in a broad range of assays." Cancer Cell 42(3): 325-327.(20240222,上海交通大学,卢敏,代雨婷)在10个p53活性实验系统中,共制备了超过10,000多个生物学样品,头对头比较了所有可获取的30余个,量化了这些恢复剂对p53突变体的功能恢复效果。(Cancer Cell丨卢敏团队分析现有p53靶向药物的有效性并提出p53恢复剂评估标准和临床建议)
Zheng, H., M. An, Y. Luo, X. Diao, W. Zhong, M. Pang, Y. Lin, J. Chen, Y. Li, Y. Kong, Y. Zhao, Y. Yin, L. Ai, J. Huang, C. Chen and T. Lin (2024). " PDGFRα+ITGA11+ fibroblasts foster early-stage cancer lymphovascular invasion and lymphatic metastasis via ITGA11-SELE interplay." Cancer Cell 42(4): 682-700.e612.(20240229,中山大学,林天歆,陈长昊)阐明了PDGFRα+ITGA11+ CAFs亚群通过ITGA11-SELE配受体互作诱导淋巴管新生,并重塑细胞外基质介导肿瘤细胞侵袭浸润淋巴管,促进早期膀胱癌脉管癌栓形成的关键分子机制,有望为早期阻断膀胱癌淋巴转移提供新的干预靶点。(Cancer Cell | 林天歆团队揭示膀胱癌脉管癌栓形成的关键分子机制)
Niu, N., X. Shen, Z. Wang, Y. Chen, Y. Weng, F. Yu, Y. Tang, P. Lu, M. Liu, L. Wang, Y. Sun, M. Yang, B. Shen, J. Jin, Z. Lu, K. Jiang, Y. Shi and J. Xue (2024). "Tumor cell-intrinsic epigenetic dysregulation shapes cancer-associated fibroblasts heterogeneity to metabolically support pancreatic cancer." Cancer Cell 42(5): 869-884.e869.(20240404,上海交通大学医学院,薛婧)在组蛋白甲基转移酶SETD2缺陷型胰腺肿瘤中鉴定出一类富脂型CAF,揭示了表观遗传元件调控肿瘤细胞-CAF交互作用的分子机制,并为SETD2缺陷型胰腺癌患者精准诊疗提供了新策略。(Cancer Cell | 薛婧团队揭示表观遗传失调调控胰腺肿瘤癌相关成纤维细胞异质性及代谢重塑)
Yang, H., J. Cheng, H. Zhuang, H. Xu, Y. Wang, T. Zhang, Y. Yang, H. Qian, Y. Lu, F. Han, L. Cao, N. Yang, R. Liu, X. Yang, J. Zhang, J. Wu and N. Zhang (2024). "Pharmacogenomic profiling of intra-tumor heterogeneity using a large organoid biobank of liver cancer." Cancer Cell 42(4): 535-551.e538.(20240408,北京大学,张宁,吴健民;河南省肿瘤医院,张建功)基于肝癌类器官生物库,进一步解析了肝癌瘤内异质性,通过大规模靶向药筛选,揭示了靶向药药敏分子分型,阐明c-Jun介导仑伐替尼耐药机制,合成PKUF-01,为肝癌的精准诊疗提供了重要线索。(Cancer Cell | 张宁/吴健民/杨兴/张建功团队揭示肝癌治疗的药敏分子分型和耐药新机制)
Lin, C.-J., X. Jin, D. Ma, C. Chen, Y. Ou-Yang, Y.-C. Pei, C.-Z. Zhou, F.-L. Qu, Y.-J. Wang, C.-L. Liu, L. Fan, X. Hu, Z.-M. Shao and Y.-Z. Jiang (2024). "Genetic interactions reveal distinct biological and therapeutic implications in breast cancer." Cancer Cell 42(4): 701-719.e712.(20240408,复旦大学,江一舟,邵志敏,胡欣)系统性绘制了全面的乳腺癌基因组变异互作网络,结合临床治疗队列及体内外模型功能性解析了基因组变异互作对乳腺癌治疗结局的影响,提出了基于基因组变异互作的精准治疗新策略。(Cancer Cell | 江一舟/邵志敏/胡欣团队功能性解析乳腺癌基因组变异互作在精准治疗中的指导价值)
Wang, W., T. Li, Y. Cheng, F. Li, S. Qi, M. Mao, J. Wu, Q. Liu, X. Zhang, X. Li, L. Zhang, H. Qi, L. Yang, K. Yang, Z. He, S. Ding, Z. Qin, Y. Yang, X. Yang, C. Luo, Y. Guo, C. Wang, X. Liu, L. Zhou, Y. Liu, W. Kong, J. Miao, S. Ye, M. Luo, L. An, L. Wang, L. Che, Q. Niu, Q. Ma, X. Zhang, Z. Zhang, R. Hu, H. Feng, Y.-F. Ping, X.-W. Bian and Y. Shi (2024). "Identification of hypoxic macrophages in glioblastoma with therapeutic potential for vasculature normalization." Cancer Cell 42(5): 815-832.e812.(20240418,陆军军医大学,卞修武,时雨,平轶芳)系统揭示了恶性胶质瘤内Mo-TAM的转录表型和空间分布异质性特征,鉴定出缺氧坏死微环境内富集的TAM缺氧亚群(Hypoxia-TAM)并证实其诱导微血管渗漏表型,阐明了靶向该亚群对胶质瘤血管正常化和提高抗肿瘤药物递送效率的治疗学意义。(Cancer Cell | 卞修武/时雨/平轶芳团队发现恶性胶质瘤内肿瘤相关巨噬细胞新亚群及其在肿瘤血管正常化中的治疗意义)
Liu, H., J. Gao, M. Feng, J. Cheng, Y. Tang, Q. Cao, Z. Zhao, Z. Meng, J. Zhang, G. Zhang, C. Zhang, M. Zhao, Y. Yan, Y. Wang, R. Xue, N. Zhang and H. Li (2024). "Integrative molecular and spatial analysis reveals evolutionary dynamics and tumor-immune interplay of in situ and invasive acral melanoma." Cancer Cell 42(6): 1067-1085.e1011.(20240516,北京大学,张宁,李航,薛瑞栋)解析了从AMis进展到iAM的克隆演化规律,建立了AM的分子分型,揭示了APOE+/CD163+巨噬细胞的空间富集状态,进一步通过实验证实该巨噬细胞亚群可通过IGF1-IGF1R互作促进肿瘤发生上皮-间质转化,最终鉴定出附属器受累和驱动突变可预测AMis的侵袭潜能,而APOE和CD163则可用于预测iAM的预后,为肢端型黑色素瘤的早期诊断和临床诊疗提供了重要依据。(Cancer Cell | 李航/张宁/薛瑞栋团队联合揭示肢端型黑色素瘤的克隆演化规律及肿瘤-免疫空间互作机制)
Zhong, J., X. Xing, Y. Gao, L. Pei, C. Lu, H. Sun, Y. Lai, K. Du, F. Xiao, Y. Yang, X. Wang, Y. Shi, F. Bai and N. Zhang (2024). "Distinct roles of TREM2 in central nervous system cancers and peripheral cancers." Cancer Cell 42(6): 968-984.e969.(20240523,中山大学,张弩;北京大学,白凡)首次发现髓系免疫细胞表达的信号枢纽分子TREM2在GBM等CNS肿瘤当中发挥免疫保护作用,打破了目前TREM2在肿瘤中起免疫抑制作用的认知,揭示了CNS肿瘤微环境特异因素介导的髓系免疫细胞表型重塑机制,以及提高TREM2表达量对重新激活抗肿瘤免疫反应的关键作用,为器官特异性肿瘤免疫治疗策略研发提供了新的理论依据。(Cancer Cell | 张弩/白凡团队合作揭示TREM2在中枢神经系统肿瘤的免疫保护作用)
Wang, Z., C. Liu, S. Zheng, Y. Yao, S. Wang, X. Wang, E. Yin, Q. Zeng, C. Zhang, G. Zhang, W. Tang, B. Zheng, L. Xue, Z. Wang, X. Feng, Y. Wang, J. Ying, Q. Xue, N. Sun and J. He (2024). "Molecular subtypes of neuroendocrine carcinomas: A cross-tissue classification framework based on five transcriptional regulators." Cancer Cell 42(6): 1106-1125.e1108. (20240523,中国医学科学院北京协和医学院肿瘤医院,赫捷,孙楠)该研究综合7个队列来源于不同组织器官的神经内分泌癌表达谱,通过泛癌整合揭示了不同起源神经内分泌癌不依赖于原发组织的分子趋同性。
Li, Y., M. Huang, M. Wang, Y. Wang, P. Deng, C. Li, J. Huang, H. Chen, Z. Wei, Q. Ouyang, J. Zhao, Y. Lu and S. Su (2024). "Tumor cells impair immunological synapse formation via central nervous system-enriched metabolite." Cancer Cell 42(6): 985-1002.e1018.(20240530,中山大学,苏士成、陆艺文)发现肿瘤细胞通过表达中枢神经系统(CNS)富集的 N-乙酰转移酶 8 样蛋白(NAT8L)及其代谢产物 N-乙酰天冬氨酸(NAA)来逃避抗肿瘤免疫反应。
Zhou, Q., Y. Pan, X. Yang, Y. Zhao, G. Han, Q. Pang, Z. Zhang, Q. Wang, J. Yao, H. Wang, W. Yang, B. Liu, Q. Chen, X. Du, K. Cai, B. Li, Y. Huang, X. Li, L. Song, W. Shi and Y.-L. Wu (2024). "Neoadjuvant SHR-1701 with or without chemotherapy in unresectable stage III non-small-cell lung cancer: A proof-of-concept, phase 2 trial." Cancer Cell 42(7): 1258-1267.e1252.(20240620,南方医科大学,吴一龙)在不可切除的Ⅲ期NSCLC中,新辅助SHR-1701联合化疗(随后进行手术或放疗)显示出有前景的抗肿瘤活性,并且安全性可耐受。研究证实1/4的患者实现了手术转化,并转化为较好的生存结局。
Wang, Y.-R., P. Wang, Z. Yan, Q. Zhou, F. Gunturkun, P. Li, Y. Hu, W. E. Wu, K. Zhao, M. Zhang, H. Lv, L. Fu, J. Jin, Q. Du, H. Wang, K. Chen, L. Qu, K. Lin, M. Iv, H. Wang, X. Sun, H. Vogel, S. Han, L. Tian, F. Wu and J. Gong (2024). "Advancing presurgical non-invasive molecular subgroup prediction in medulloblastoma using artificial intelligence and MRI signatures." Cancer Cell 42(7): 1239-1257.e1237.(20240627,斯坦福大学,王嫣然;北京天坛医院,宫剑)提出了一种全新的基于人工智能的手术前核磁共振分子亚型诊断方法,该方法提供了无创低成本的分子亚型预测方案。这一突破性进展为肿瘤无创分子亚型诊断,以及髓母细胞瘤的精准医疗开辟了新途径。(Cancer Cell丨王嫣然/宫剑等提出一种全新的基于人工智能的手术前核磁共振分子亚型诊断方法助力髓母细胞瘤精准医疗)
Zhou, C., C. Li, L. Luo, X. Li, K. Jia, N. He, S. Mao, W. Wang, C. Shao, X. Liu, K. Huang, Y. Yu, X. Cai, Y. Chen, Z. Dai, W. Li, J. Yu, J. Li, F. Shen, Z. Wang, F. He, X. Sun, R. Mao, W. Shi, J. Zhang, T. Jiang, Z. Zhang, F. Li and S. Ren (2024). "Anti-tumor efficacy of HRS-4642 and its potential combination with proteasome inhibition in KRAS G12D-mutant cancer." Cancer Cell 42(7): 1286-1300.e1288.(20240627,同济大学,任胜祥,周彩存,蒋涛;复旦大学,李飞;上海恒瑞医药有限公司,张喆)提供了首个临床有效KRAS G12D特异性抑制剂——HRS-4642,及其与蛋白酶体抑制剂联合的治疗新策略。(Cancer Cell|任胜祥/周彩存/李飞/张喆/蒋涛合作提供KRAS G12D突变靶向治疗新策略)
Chen, Y., D. Wang, Y. Li, L. Qi, W. Si, Y. Bo, X. Chen, Z. Ye, H. Fan, B. Liu, C. Liu, L. Zhang, X. Zhang, Z. Li, L. Zhu, A. Wu and Z. Zhang (2024). "Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in colorectal cancer." Cancer Cell 42(7): 1268-1285.e1267.(20240708,北京大学,张泽民;北京肿瘤医院,武爱文)动态追踪了结直肠癌患者在免疫治疗下原位癌灶及外周系统的时空变化,通过系统性鉴定“细胞程序”揭示了肿瘤微环境中多种细胞类型在免疫治疗过程中的协同演化规律,进一步解析了外周免疫系统对免疫治疗疗效的关键作用,建立了基线水平外周CD8 T细胞的激活状态与患者疗效的关联,为理解免疫治疗响应差异提供了新的视角。(Cancer Cell丨张泽民/武爱文合作团队解析辅助免疫治疗前后不同响应人群的细胞和分子动态变化图谱)
You, S., S. Li, L. Zeng, J. Song, Z. Li, W. Li, H. Ni, X. Xiao, W. Deng, H. Li, W. Lin, C. Liang, Y. Zheng, S.-C. Cheng, N. Xiao, M. Tong, R. Yu, J. Huang, H. Huang, H. Xu, J. Han, J. Ren and K. Mao (2024). "Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity." Cancer Cell 42(8): 1415-1433.e1412.(20240718,厦门大学,毛开睿)揭示了肿瘤微环境中Treg独特的空间定位及其抑制抗肿瘤免疫反应的新机制。(Cancer Cell丨毛开睿团队空间解析肿瘤抑制性免疫微环境)
Lv, J., L.-X. Xu, Z.-X. Li, L. Lin, C.-F. Wu, T.-Q. Quan, Z.-C. Zhen, W.-F. Li, L.-L. Tang, Y.-P. Mao, L. Chen, R. Guo, L.-L. Zhang, X.-L. Ai, S.-Y. Wu, M.-Y. Hao, D. Wei, J.-B. Li, J. Ma, Y.-P. Chen, G.-Q. Zhou and Y. Sun (2024). "Longitudinal on-treatment circulating tumor DNA as a biomarker for real-time dynamic risk monitoring in cancer patients: The EP-SEASON study." Cancer Cell 42(8): 1401-1414.e1404.(20240725,中山大学,孙颖,周冠群,陈雨沛,马骏)以鼻咽癌作为研究模型,通过动态追踪患者血浆中的游离Epstein-Barr病毒DNA(cfEBV DNA,一种循环肿瘤DNA)成功实现了对患者治疗响应性和复发转移风险的实时监测,为开展个体化治疗提供了可靠的生物标志物。(Cancer Cell | 孙颖/马骏/吕佳蔚团队实现利用血浆EBV DNA实时监测鼻咽癌疗效和预后)
Xiao, W.-W., G. Chen, Y.-H. Gao, J.-Z. Lin, X.-J. Wu, H.-L. Luo, Z.-H. Lu, Q.-X. Wang, R. Sun, P.-Q. Cai, C.-M. Zhu, M. Liu, J.-B. Li, Y.-R. Wang, Y. Jin, F. Wang, H.-T. Luo, C.-L. Li, Z.-Z. Pan and R.-H. Xu (2024). "Effect of neoadjuvant chemoradiotherapy with or without PD-1 antibody sintilimab in pMMR locally advanced rectal cancer: A randomized clinical trial." Cancer Cell 42(9): 1570-1581.e1574.(20240801,中山大学,徐瑞华)评估了新辅助放化疗联合信迪利单抗(sintilimab)对比新辅助放化疗治疗错配修复完整(pMMR)局部进展期直肠癌患者的疗效和安全性,并对疗效相关的指标进行了探索性分析。(Cancer Cell丨徐瑞华团队证实新辅助放化疗联合信迪利单抗较新辅助放化疗显著提升pMMR局部进展期直肠癌的完全缓解率)
Zhang, Y., G. Liu, Q. Zeng, W. Wu, K. Lei, C. Zhang, M. Tang, Y. Zhang, X. Xiang, L. Tan, R. Cui, S. Qin, X. Song, C. Yin, Z. Chen and M. Kuang (2024). "CCL19-producing fibroblasts promote tertiary lymphoid structure formation enhancing anti-tumor IgG response in colorectal cancer liver metastasis." Cancer Cell 42(8): 1370-1385.e1379.(20240812,中山大学,匡铭,陈志航,尹长军)揭示了TLSs在CRLM中的分布和临床意义,发现了CCL19+成纤维细胞在TLS形成中的重要作用,并证明了TLSs原位产生靶向肿瘤的抗体可以介导抗肿瘤免疫,为抗肿瘤免疫研究提供了新的研究方向,为研发诊断和治疗结直肠癌肝转移的药物提供了新的思路。(Cancer Cell丨匡铭/陈志航/尹长军揭示结直肠癌肝转移中三级淋巴结构产生靶向肿瘤的抗体并介导抗肿瘤免疫新方向)
Sun, Y., X. Zhang, D. Hang, H. C.-H. Lau, J. Du, C. Liu, M. Xie, Y. Pan, L. Wang, C. Liang, X. Zhou, D. Chen, J. Rong, Z. Zhao, A. H.-K. Cheung, Y. Wu, H. Gou, C. C. Wong, L. Du, J. Deng, Z. Hu, H. Shen, Y. Miao and J. Yu (2024). "Integrative plasma and fecal metabolomics identify functional metabolites in adenoma-colorectal cancer progression and as early diagnostic biomarkers." Cancer Cell 42(8): 1386-1400.e1388.(20240812,香港中文大学,于君;昆明医科大学,缪应雷;南京医科大学,沈洪兵)合作鉴定出了腺瘤-结直肠癌进展中的功能性代谢物及早期诊断生物标志物。(Cancer Cell封面文章 | 于君/缪应雷/沈洪兵合作鉴定出腺瘤-结直肠癌进展中的功能性代谢物及早期诊断生物标志物)
Xu, J., R. Wan, Y. Cai, S. Cai, L. Wu, B. Li, J. Duan, Y. Cheng, X. Li, X. Wang, L. Han, X. Wu, Y. Fan, Y. Yu, D. Lv, J. Shi, J. Huang, S. Zhou, B. Han, G. Sun, Q. Guo, Y. Ji, X. Zhu, S. Hu, W. Zhang, Q. Wang, Y. Jia, Z. Wang, Y. Song, J. Wu, M. Shi, X. Li, Z. Han, Y. Liu, Z. Yu, A.-W. Liu, X. Wang, C. Zhou, D. Zhong, L. Miao, Z. Zhang, H. Zhao, J. Yang, D. Wang, Y. Wang, Q. Li, X. Zhang, M. Ji, Z. Yang, J. Cui, B. Gao, B. Wang, H. Liu, L. Nie, M. He, S. Jin, W. Gu, Y. Shu, T. Zhou, J. Feng, X. Yang, C. Huang, B. Zhu, Y. Yao, J. Yu, S. Yao, R. Shen, Z. Wang and J. Wang (2024). "Circulating tumor DNA-based stratification strategy for chemotherapy plus PD-1 inhibitor in advanced non-small-cell lung cancer." Cancer Cell 42(9): 1598-1613.e1594.(20240909,中国医学科学院肿瘤医院,王洁,王志杰)对全国多中心、III期、随机对照临床研究(CHOICE-01)进行了动态标本的前瞻性收集及全景基因组特征的整合分析,建立了一种基于ctDNA的整合型基因组特征的外周血基因组免疫分型(blood-based genomic immune subtypes,bGIS)方法,为晚期NSCLC一线免疫联合化疗精细化分层提供了新策略,并为未来基于该分层策略的进一步前瞻性研究指明了方向。(Cancer Cell | 王洁团队构建基于ctDNA的免疫分型,助力非小细胞肺癌精准免疫治疗决策)
Wang, X., Y. Fang, W. Liang, C. C. Wong, H. Qin, Y. Gao, M. Liang, L. Song, Y. Zhang, M. Fan, C. Liu, H. C.-H. Lau, L. Xu, X. Li, W. Song, J. Wang, N. Wang, T. Yang, M. Mo, X. Zhang, J. Fang, B. Liao, J. J. Y. Sung and J. Yu (2024). "Fusobacterium nucleatum facilitates anti-PD-1 therapy in microsatellite stable colorectal cancer." Cancer Cell 42(10): 1729-1746.e1728. (20240919,中山大学,于君)该研究提示了,Fn 丰度可能是预测微卫星稳定型结直肠癌中anti-PD-1治疗效果的生物标志物,并表明提高肿瘤内Fn 丰度及其代谢产物丁酸,有望成为改善anti-PD-1治疗微卫星稳定型结直肠癌效果的潜在策略。(Cancer Cell丨于君团队揭示具核梭杆菌改善微卫星稳定型结直肠癌anti-PD-1治疗响应性)
Gao, Y., J. Li, W. Cheng, T. Diao, H. Liu, Y. Bo, C. Liu, W. Zhou, M. Chen, Y. Zhang, Z. Liu, W. Han, R. Chen, J. Peng, L. Zhu, W. Hou and Z. Zhang (2024). "Cross-tissue human fibroblast atlas reveals myofibroblast subtypes with distinct roles in immune modulation." Cancer Cell 42(10): 1764-1783.e1710. (20240919,北京大学,张泽民;广东医科大学,侯文洪)基于健康、纤维化、炎症以及癌症等多种疾病状态下的11种组织的单细胞数据,构建了涵盖517个人类样本、269,899个成纤维细胞的图谱,并鉴定出20种成纤维细胞亚型,揭示了成纤维细胞未被充分认识的转录异质性,其中发现了4类具有独特表型的肌成纤维细胞亚型。(Cancer Cell | 张泽民团队通过跨组织单细胞多组学揭示肌成纤维细胞的多样化免疫调节特征)
Shang, X., Y. Xie, J. Yu, C. Zhang, G. Zhao, F. Liang, L. Liu, W. Zhang, R. Li, W. Yu, J. Yue, C. Chen, X. Duan, Z. Ma, Z. Chen, Y. Xiong, F. Yang, J. Xiao, R. Zhang, P. Liu, Y. Cheng, F. Cao, F. Guo, G. Liu, B. Meng, D. Zhou, Y. Sun, X. Ren, J. Yu, J. Hao and H. Jiang (2024). "A prospective study of neoadjuvant pembrolizumab plus chemotherapy for resectable esophageal squamous cell carcinoma: The Keystone-001 trial." Cancer Cell 42(10): 1747-1763.e1747.(20241014,天津医科大学,任秀宝,余俊,郝继辉,姜宏景)在一项II期临床试验中展示了新辅助药物帕博利珠单抗联合化疗对局部晚期、可切除食管鳞状细胞癌(ESCC)患者的疗效和安全性。
Fu, M., J. Zhao, L. Zhang, Z. Sheng, X. Li, F. Qiu, Y. Feng, M. You, H. Xu, J. Zhang, R. Zeng, Y. Huang, C. Li, W. Chen, Z. Chen, H. Peng, L. Li, Y. Wu, D. Ye, Y. Chi, W. Hua and Y. Mao (2024). "Overcoming tyrosine kinase inhibitor resistance in lung cancer brain metastasis with CTLA4 blockade." Cancer Cell.(20241017,复旦大学,毛颖,花玮,迟喻丹)揭示了TKI靶向药物奥希替尼在治疗过程中的耐药机制。奥希替尼不仅能够显著提升T细胞在肿瘤中的浸润度,还促使免疫检查点CTLA4的表达上调。这种机制的出现最终导致了肿瘤细胞通过免疫逃逸现象躲避T细胞的攻击。
Yang C, Geng H, Yang X, Ji S, Liu Z, Feng H, Li Q, Zhang T, Zhang S, Ma X, Zhu C, Xu N, Xia Y, Li Y, Wang H, Yu C, Du S, Miao B, Xu L, Wang H, Cao Y, Li B, Zhu L, Tang X, Zhang H, Zhu C, Huang Z, Leng C, Hu H, Chen X, Yuan S, Jin G, Bernards R, Sun C, Zheng Q, Qin W, Gao Q, Wang C.(2024) "Targeting the immune privilege of tumor-initiating cells to enhance cancer immunotherapy." Cancer Cell.(20241107,上海市肿瘤研究所,王存,覃文新;复旦大学,高强;上海交通大学,郑铨;德国癌症研究中心,孙崇)结合类器官与单细胞多组学技术,全面分析了十余种肿瘤起始细胞标志物分子,发现CD49f高表达肝癌细胞通过CXCL2-CXCR2轴招募中性粒细胞,形成独特的免疫抑制微环境。联合靶向PD-1和CD155的治疗策略不仅能清除CD49f高表达肝癌起始细胞,还能破坏其依赖的免疫抑制微环境,从而显著提高免疫治疗疗效。(Cancer Cell│覃文新/王存/高强等合作揭示CD49f阳性肝癌细胞亚群免疫逃逸机制和精准治疗策略)
Huang CX, Lao XM, Wang XY, Ren YZ, Lu YT, Shi W, Wang YZ, Wu CY, Xu L, Chen MS, Gao Q, Liu L, Wei Y, Kuang DM. "Pericancerous cross-presentation to cytotoxic T lymphocytes impairs immunotherapeutic efficacy in hepatocellular carcinoma." Cancer Cell.(20241114,中山大学,邝栋明,魏瑗)结合多队列肝癌免疫治疗样本与单细胞测序、TCR测序和空间转录组等多组学数据分析和体内外实验模型,揭示了癌周巨噬细胞通过抗原交叉呈递介导肿瘤反应性CTL(CD103+ CTL)在癌周区域滞留,这些滞留的效应CD103+ CTL反过来激活巨噬细胞的致病性炎症,最终导致肿瘤进展和免疫治疗耐受。(Cancer Cell丨邝栋明/魏瑗团队揭示癌周交叉呈递触发致病性炎症削弱免疫治疗疗效的机制和治疗新策略)
Qiu, Y., Y. Su, E. Xie, H. Cheng, J. Du, Y. Xu, X. Pan, Z. Wang, D. G. Chen, H. Zhu, P. D. Greenberg and G. Li "Mannose metabolism reshapes T cell differentiation to enhance anti-tumor immunity." Cancer Cell.(20241205,中国医学科学院系统医学研究院,李贵登;Fred Hutchinson癌症研究中心,Philip D. Greenberg)首次揭示了甘露糖代谢在T细胞分化中的调控作用,并建立了一种体外高效诱导“干性样”T细胞的新方法。(专家点评Cancer Cell丨李贵登团队等建立一种体外高效诱导“干性样”T细胞的新方法)
Yang, Z., X. Liu, J. Zhu, Y. Chai, B. Cong, B. Li, W. Gao, Y. Hu, M. Wen, Y. Liu, L. Fu and X. Cao "Inhibiting intracellular CD28 in cancer cells enhances antitumor immunity and overcomes anti-PD-1 resistance via targeting PD-L1." Cancer Cell.(20241212,南开大学,曹雪涛)发现乳腺癌细胞胞内CD28可以与Cd274 mRNA结合,并招募SNRPB2以增强Cd274 mRNA稳定性,促进瘤细胞PD-L1表达,进而促进PD-1抗体治疗的耐药性,而靶向抑制瘤细胞胞内CD28能够克服PD-1抗体治疗的耐药性。(Cancer Cell | 曹雪涛团队揭示肿瘤细胞通过其胞内CD28促进免疫逃逸)