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Tumor-infiltrating lymphocytes: A new hope 肿瘤浸润淋巴细胞：新希望
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-07-18 DOI: 10.1016/j.ccell.2024.06.015
{"title":"Tumor-infiltrating lymphocytes: A new hope","authors":"","doi":"10.1016/j.ccell.2024.06.015","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.06.015","url":null,"abstract":"<p>Tumor-infiltrating lymphocytes (TILs) can be massively expanded from resected tumors and used as a cellular treatment for advanced malignancies. TILs require a preparative non-myeloablative chemotherapy followed by an abbreviated course of interleukin-2. Here, we review the historical development of TIL therapy and discuss potential solutions to ongoing roadblocks that may result in broader and improved efficacy for patients afflicted with treatment-refractory, advanced cancer.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726366","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Transcription factor dependencies identify BAF-dependent cancers 转录因子依赖性确定了 BAF 依赖性癌症
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-07-18 DOI: 10.1016/j.ccell.2024.06.013
{"title":"Transcription factor dependencies identify BAF-dependent cancers","authors":"","doi":"10.1016/j.ccell.2024.06.013","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.06.013","url":null,"abstract":"<p>In <em>Cancer Cell</em>, Bolomsky et al., Duplaquet et al., and He et al. identify cancers that are dependent on the BAF chromatin remodeling complex, specifically IRF4-driven multiple myeloma and POU2F3-subtype small cell lung cancer, highlighting potential therapeutic applications for BAF complex inhibitors/degraders.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726363","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer 哺乳动物 SWI/SNF 复合物活性调控 POU2F3 并构成小细胞肺癌的靶向依赖性
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-07-18 DOI: 10.1016/j.ccell.2024.06.012
{"title":"Mammalian SWI/SNF complex activity regulates POU2F3 and constitutes a targetable dependency in small cell lung cancer","authors":"","doi":"10.1016/j.ccell.2024.06.012","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.06.012","url":null,"abstract":"<p>Small cell lung cancers (SCLCs) are composed of heterogeneous subtypes marked by lineage-specific transcription factors, including ASCL1, NEUROD1, and POU2F3. POU2F3-positive SCLCs, ∼12% of all cases, are uniquely dependent on POU2F3 itself; as such, approaches to attenuate POU2F3 expression may represent new therapeutic opportunities. Here using genome-scale screens for regulators of POU2F3 expression and SCLC proliferation, we define mSWI/SNF complexes as top dependencies specific to POU2F3-positive SCLC. Notably, chemical disruption of mSWI/SNF ATPase activity attenuates proliferation of all POU2F3-positive SCLCs, while disruption of non-canonical BAF (ncBAF) via BRD9 degradation is effective in pure non-neuroendocrine POU2F3-SCLCs. mSWI/SNF targets to and maintains accessibility over gene loci central to POU2F3-mediated gene regulatory networks. Finally, clinical-grade pharmacologic disruption of SMARCA4/2 ATPases and BRD9 decreases POU2F3-SCLC tumor growth and increases survival <em>in vivo</em>. These results demonstrate mSWI/SNF-mediated governance of the POU2F3 oncogenic program and suggest mSWI/SNF inhibition as a therapeutic strategy for POU2F3-positive SCLCs.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726365","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity 淋巴定位的Treg-mregDC串扰限制了抗原贩运并抑制了抗肿瘤免疫力
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-07-18 DOI: 10.1016/j.ccell.2024.06.014
{"title":"Lymphatic-localized Treg-mregDC crosstalk limits antigen trafficking and restrains anti-tumor immunity","authors":"","doi":"10.1016/j.ccell.2024.06.014","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.06.014","url":null,"abstract":"<p>The tumor microenvironment (TME) has a significant impact on tumor growth and immunotherapy efficacies. However, the precise cellular interactions and spatial organizations within the TME that drive these effects remain elusive. Using advanced multiplex imaging techniques, we have discovered that regulatory T cells (Tregs) accumulate around lymphatic vessels in the peripheral tumor stroma. This localized accumulation is facilitated by mature dendritic cells enriched in immunoregulatory molecules (mregDCs), which promote chemotaxis of Tregs, establishing a peri-lymphatic Treg-mregDC niche. Within this niche, mregDCs facilitate Treg activation, which in turn restrains the trafficking of tumor antigens to the draining mesenteric lymph nodes, thereby impeding the initiation of anti-tumor adaptive immune responses. Disrupting Treg recruitment to mregDCs inhibits tumor progression. Our study provides valuable insights into the organization of TME and how local crosstalk between lymphoid and myeloid cells suppresses anti-tumor immune responses.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726367","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Targeting the mSWI/SNF complex in POU2F-POU2AF transcription factor-driven malignancies 在 POU2F-POU2AF 转录因子驱动的恶性肿瘤中瞄准 mSWI/SNF 复合物
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-07-18 DOI: 10.1016/j.ccell.2024.06.006
{"title":"Targeting the mSWI/SNF complex in POU2F-POU2AF transcription factor-driven malignancies","authors":"","doi":"10.1016/j.ccell.2024.06.006","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.06.006","url":null,"abstract":"<p>The POU2F3-POU2AF2/3 transcription factor complex is the master regulator of the tuft cell lineage and tuft cell-like small cell lung cancer (SCLC). Here, we identify a specific dependence of the POU2F3 molecular subtype of SCLC (SCLC-P) on the activity of the mammalian switch/sucrose non-fermentable (mSWI/SNF) chromatin remodeling complex. Treatment of SCLC-P cells with a proteolysis targeting chimera (PROTAC) degrader of mSWI/SNF ATPases evicts POU2F3 and its coactivators from chromatin and attenuates downstream signaling. B cell malignancies which are dependent on the POU2F1/2 cofactor, POU2AF1, are also sensitive to mSWI/SNF ATPase degraders, with treatment leading to chromatin eviction of POU2AF1 and IRF4 and decreased IRF4 signaling in multiple myeloma cells. An orally bioavailable mSWI/SNF ATPase degrader significantly inhibits tumor growth in preclinical models of SCLC-P and multiple myeloma without signs of toxicity. This study suggests that POU2F-POU2AF-driven malignancies have an intrinsic dependence on the mSWI/SNF complex, representing a therapeutic vulnerability.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726364","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Perilymphatic regulatory T cell-dendritic cell interactions represent a novel axis of immunosuppression in cancer 淋巴周围调节性 T 细胞-树突状细胞相互作用是癌症免疫抑制的新轴心
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-07-18 DOI: 10.1016/j.ccell.2024.06.016
{"title":"Perilymphatic regulatory T cell-dendritic cell interactions represent a novel axis of immunosuppression in cancer","authors":"","doi":"10.1016/j.ccell.2024.06.016","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.06.016","url":null,"abstract":"<p>Dendritic cells are critical inducers of adaptive anti-tumor immunity. However, their maturation, activation, and migration are often compromised in the tumor microenvironment. In this issue, You et al. demonstrate a novel axis of suppression of dendritic cell function mediated by interaction with regulatory T cells in perilymphatic niches.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-07-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141726372","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution 用循环肿瘤细胞外囊泡监测转移性前列腺癌基因组学和转录组学演变
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-07-08 DOI: 10.1016/j.ccell.2024.06.003
Irene Casanova-Salas, Daniel Aguilar, Sarai Cordoba-Terreros, Laura Agundez, Julian Brandariz, Nicolas Herranz, Alba Mas, Macarena Gonzalez, Rafael Morales-Barrera, Alexandre Sierra, Mario Soriano-Navarro, Pablo Cresta, Gisela Mir, Sara Simonetti, Gonçalo Rodrigues, Sara Arce-Gallego, Luisa Delgado-Serrano, Irene Agustí, Elena Castellano-Sanz, Richard Mast, Joaquin Mateo
{"title":"Circulating tumor extracellular vesicles to monitor metastatic prostate cancer genomics and transcriptomic evolution","authors":"Irene Casanova-Salas, Daniel Aguilar, Sarai Cordoba-Terreros, Laura Agundez, Julian Brandariz, Nicolas Herranz, Alba Mas, Macarena Gonzalez, Rafael Morales-Barrera, Alexandre Sierra, Mario Soriano-Navarro, Pablo Cresta, Gisela Mir, Sara Simonetti, Gonçalo Rodrigues, Sara Arce-Gallego, Luisa Delgado-Serrano, Irene Agustí, Elena Castellano-Sanz, Richard Mast, Joaquin Mateo","doi":"10.1016/j.ccell.2024.06.003","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.06.003","url":null,"abstract":"<p>Extracellular vesicles (EVs) secreted by tumors are abundant in plasma, but their potential for interrogating the molecular features of tumors through multi-omic profiling remains widely unexplored. Genomic and transcriptomic profiling of circulating EV-DNA and EV-RNA isolated from <em>in vitro</em> and <em>in vivo</em> models of metastatic prostate cancer (mPC) reveal a high contribution of tumor material to EV-loaded DNA/RNA, validating the findings in two cohorts of longitudinal plasma samples collected from patients during androgen receptor signaling inhibitor (ARSI) or taxane-based therapy. EV-DNA genomic features recapitulate matched-patient biopsies and circulating tumor DNA (ctDNA) and associate with clinical progression. We develop a novel approach to enable transcriptomic profiling of EV-RNA (RExCuE). We report how the transcriptome of circulating EVs is enriched for tumor-associated transcripts, captures certain patient and tumor features, and reflects on-therapy tumor adaptation changes. Altogether, we show that EV profiling enables longitudinal transcriptomic and genomic profiling of mPC in liquid biopsy.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561683","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in colorectal cancer 时空单细胞分析解码结直肠癌免疫疗法不同反应的细胞动力学基础
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-07-08 DOI: 10.1016/j.ccell.2024.06.009
Yuqing Chen, Dongfang Wang, Yingjie Li, Lu Qi, Wen Si, Yufei Bo, Xueyan Chen, Zhaochen Ye, Hongtao Fan, Baolin Liu, Chang Liu, Li Zhang, Xiaoyan Zhang, Zhongwu Li, Linna Zhu, Aiwen Wu, Zemin Zhang
{"title":"Spatiotemporal single-cell analysis decodes cellular dynamics underlying different responses to immunotherapy in colorectal cancer","authors":"Yuqing Chen, Dongfang Wang, Yingjie Li, Lu Qi, Wen Si, Yufei Bo, Xueyan Chen, Zhaochen Ye, Hongtao Fan, Baolin Liu, Chang Liu, Li Zhang, Xiaoyan Zhang, Zhongwu Li, Linna Zhu, Aiwen Wu, Zemin Zhang","doi":"10.1016/j.ccell.2024.06.009","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.06.009","url":null,"abstract":"<p>Expanding the efficacy of immune checkpoint blockade (ICB) in colorectal cancer (CRC) presses for a comprehensive understanding of treatment responsiveness. Here, we analyze multiple sequential single-cell samples from 22 patients undergoing PD-1 blockade to map the evolution of local and systemic immunity of CRC patients. In tumors, we identify coordinated cellular programs exhibiting distinct response associations. Specifically, exhausted T (Tex) or tumor-reactive-like CD8<sup>+</sup> T (Ttr-like) cells are closely related to treatment efficacy, and Tex cells show correlated proportion changes with multiple other tumor-enriched cell types following PD-1 blockade. In addition, we reveal the less-exhausted phenotype of blood-associated Ttr-like cells in tumors and find that their higher abundance suggests better treatment outcomes. Finally, a higher major histocompatibility complex (MHC) II-related signature in circulating CD8<sup>+</sup> T cells at baseline is linked to superior responses. Our study provides insights into the spatiotemporal cellular dynamics following neoadjuvant PD-1 blockade in CRC.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561681","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Immune cell triads reprogram exhausted CD8+ T cells for effective tumor elimination 免疫细胞三元组对衰竭的 CD8+ T 细胞进行重编程，从而有效消除肿瘤
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-07-08 DOI: 10.1016/j.ccell.2024.06.010
Veronica Lise, Ines Malenica, Rahul Roychoudhuri, Enrico Lugli
{"title":"Immune cell triads reprogram exhausted CD8+ T cells for effective tumor elimination","authors":"Veronica Lise, Ines Malenica, Rahul Roychoudhuri, Enrico Lugli","doi":"10.1016/j.ccell.2024.06.010","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.06.010","url":null,"abstract":"<p>In this issue of <em>Cancer Cell</em>, Espinosa-Carrasco <em>et al</em>. show that the efficacy of cancer immunotherapies depends upon the formation of intratumoral immune triads between antigen-presenting cells and antigen-specific CD4<sup>+</sup> and CD8<sup>+</sup> T cells. This interaction reprograms tumor-specific CD8<sup>+</sup> T cells to exert potent effector functions and eradicate established solid tumors.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561677","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
Casting a wider net: The clinical potential of EV transcriptomics in multi-analyte liquid biopsy 撒下更大的网：EV转录组学在多分析物液体活检中的临床潜力
IF 50.3 1区 医学
Cancer Cell Pub Date : 2024-07-08 DOI: 10.1016/j.ccell.2024.06.007
Yari Ciani, Caterina Nardella, Francesca Demichelis
{"title":"Casting a wider net: The clinical potential of EV transcriptomics in multi-analyte liquid biopsy","authors":"Yari Ciani, Caterina Nardella, Francesca Demichelis","doi":"10.1016/j.ccell.2024.06.007","DOIUrl":"https://doi.org/10.1016/j.ccell.2024.06.007","url":null,"abstract":"<p>Cancer cells release cell-free DNA (cfDNA) and extracellular vesicles (EVs) into the bloodstream, allowing disease non-invasive monitoring. In this issue of <em>Cancer Cell</em>, Casanova-Salas et al. analyze cfDNA, EV-DNA, and EV-RNA in prostate cancer longitudinal cohorts treated with androgen receptor signaling inhibitors and taxanes, identifying signals reflecting tumor adaptation processes.</p>","PeriodicalId":9670,"journal":{"name":"Cancer Cell","volume":null,"pages":null},"PeriodicalIF":50.3,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141561680","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
引用次数: 0
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