المؤلفون: Dingzhi Huang, Gen Lin, Qian Chu, Yi Hu, Jun Wang, Zhijie Wang, Fan Yang, Wenzhao Zhong, Chengzhi Zhou, Bo Zhu, Xinghao Ai, Baoshan Cao, Yabing Cao, Mingqiu Chen, Xiaohui Chen, Tianqing Chu, Jianchun Duan, Yun Fan, Yong Fang, Shuitu Feng, Weineng Feng, Hui Guo, Chengbo Han, Yong He, Shaodong Hong, Jie Hu, Meijuan Huang, Yan Huang, Da Jiang, Kan Jiang, Richeng Jiang, Bo Jin, Shi Jin, Jisheng Li, Min Li, Ziming Li, Chao Li, Jie Lin, Anwen Liu, Si‐Yang Maggie Liu, Yutao Liu, Zhefeng Liu, Zhe Liu, Zhenhua Liu, Zhentian Liu, Zhigang Liu, Yuping Lu, Tangfeng Lv, Zhiyong Ma, Qian Miao, Min Peng, Xingxiang Pu, Xiu Bao Ren, Jianzhen Shan, Jinlu Shan, Peng Shen, Bo Shen, Meiqi Shi, Yong Song, Zhengbo Song, ChunXia Su, Jianguo Sun, Panwen Tian, Jinliang Wang, Feng Wang, Huijuan Wang, Jialei Wang, Qian Wang, Wenxian Wang, Yan Wang, Lin Wu, Fang Wu, Yang Xia, Congying Xie, Conghua Xie, Tao Xin, Jianping Xiong, Haipeng Xu, Song Xu, Yiquan Xu, Bin Xu, Chunwei Xu, Xiaolong Yan, Zhenzhou Yang, Wenxiu Yao, Yao Yu, Ye Feng, Zongyang Yu, Yongfeng Yu, Dongsheng Yue, Haibo Zhang, HongMei Zhang, Li Zhang, Longfeng Zhang, Qiuyu Zhang, Tongmei Zhang, Bicheng Zhang, Jun Zhao, Mingfang Zhao, Xiaobin Zheng, Fengqiao Zhong, Jin Zhou, Penghui Zhou, Zhengfei Zhu, Juntao Zou, Zihua Zou

المصدر: Thoracic Cancer, Vol 14, Iss 34, Pp 3421-3429 (2023)

مصطلحات موضوعية: immunotherapy, NSCLC, secondary resistance, Neoplasms. Tumors. Oncology. Including cancer and carcinogens, RC254-282

الوصف: Abstract Immune checkpoint inhibitors (PD‐1/PD‐L1 and CTLA‐4 blockade) have revolutionized the treatment landscape in non‐small cell lung cancer (NSCLC). Secondary resistance to immunotherapy (IO), which poses a substantial challenge in clinical settings, occurs in several initial responders. Currently, new treatment approaches have been extensively evaluated in investigational studies for these patients to tackle this difficult problem; however, the lack of consistency in clinical definition, uniform criteria for enrollment in clinical trials, and interpretation of results remain significant hurdles to progress. Thus, our expert panel comprehensively synthesized data from current studies to propose a practical clinical definition of secondary resistance to immunotherapy in NSCLC in metastatic and neoadjuvant settings. In addition to patients who received IO alone (including IO‐IO combinations), we also generated a definition for patients treated with chemotherapy plus IO. This consensus aimed to provide guidance for clinical trial design and facilitate future discussions with investigators. It should be noted that additional updates in this consensus are required when new data is available.

وصف الملف: electronic resource

العلاقة: https://doaj.org/toc/1759-7706Test; https://doaj.org/toc/1759-7714Test

الوصول الحر: https://doaj.org/article/bdd49d5369d24d70bad9a053f8310938Test

المؤلفون: Xinlong Zheng, Kan Jiang, Weijin Xiao, Dongqiang Zeng, Wenying Peng, Jing Bai, Xiaohui Chen, Pansong Li, Longfeng Zhang, Xiaobin Zheng, Qian Miao, Haibo Wang, Shiwen Wu, Yiquan Xu, Haipeng Xu, Chao Li, Lifeng Li, Xuan Gao, Suya Zheng, Junhui Li, Deqiang Wang, Zhipeng Zhou, Xuefeng Xia, Shanshan Yang, Yujing Li, Zhaolei Cui, Qiuyu Zhang, Ling Chen, Xiandong Lin, Gen Lin

المصدر: Frontiers in Immunology, Vol 13 (2022)

مصطلحات موضوعية: CD8+ T cell, cancer-associated fibroblast, prognostic biomarker, predictive biomarker, immunotherapy, Immunologic diseases. Allergy, RC581-607

الوصف: BackgroundCancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) are critical for immune suppression by restricting immune cell infiltration in the tumor stromal zones from penetrating tumor islands and changing their function status, particularly for CD8+ T cells. However, assessing and quantifying the impact of CAFs on immune cells and investigating how this impact is related to clinical outcomes, especially the efficacy of immunotherapy, remain unclear.Materials and methodsThe TME was characterized using immunohistochemical (IHC) analysis using a large-scale sample size of gene expression profiles. The CD8+ T cell/CAF ratio (CFR) association with survival was investigated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) lung cancer cohorts. The correlation between CFR and immunotherapeutic efficacy was computed in five independent cohorts. The correlation between CFR and objective response rates (ORRs) following pembrolizumab monotherapy was investigated in 20 solid tumor types. To facilitate clinical translation, the IHC-detected CD8/α-SMA ratio was applied as an immunotherapeutic predictive biomarker in a real-world lung cancer cohort.ResultsCompared with normal tissue, CAFs were enriched in cancer tissue, and the amount of CAFs was overwhelmingly higher than that in other immune cells. CAFs are positively correlated with the extent of immune infiltration. A higher CFR was strongly associated with improved survival in lung cancer, melanoma, and urothelial cancer immunotherapy cohorts. Within most cohorts, there was no clear evidence for an association between CFR and programmed death-ligand 1 (PD-L1) or tumor mutational burden (TMB). Compared with TMB and PD-L1, a higher correlation coefficient was observed between CFR and the ORR following pembrolizumab monotherapy in 20 solid tumor types (Spearman’s r = 0.69 vs. 0.44 and 0.21). In a real-world cohort, patients with a high CFR detected by IHC benefited considerably from immunotherapy as compared with those with a low CFR (hazard ratio, 0.37; 95% confidence interval, 0.19–0.75; p < 0.001).ConclusionsCFR is a newly found and simple parameter that can be used for identifying patients unlikely to benefit from immunotherapy. Future studies are needed to confirm this finding.

وصف الملف: electronic resource

العلاقة: https://www.frontiersin.org/articles/10.3389/fimmu.2022.974265/fullTest; https://doaj.org/toc/1664-3224Test

الوصول الحر: https://doaj.org/article/498279893fb04ef4899aa04420545cedTest

المؤلفون: Chao Li, Xiaobin Zheng, Pansong Li, Huijuan Wang, Jie Hu, Lin Wu, Zhijie Wang, Hui Guo, Fang Wu, Wen‐Zhao Zhong, Chengzhi Zhou, Qian Chu, Jun Zhao, Xuejun Zheng, Weijin Xiao, Weifeng Zhu, Longfeng Zhang, Qian Li, Kan Jiang, Miao Qin, Bingcheng Wu, Yang Xu, Shiwen Wu, Haibo Wang, Shanshan Yang, Yujing Li, Xuefeng Xia, Xin Yi, Cheng Huang, Bo Zhu, Gen Lin

مصطلحات موضوعية: Cancer Immunotherapy, Oncology, Medicine, Health Sciences, Advancements in Lung Cancer Research, Pulmonary and Respiratory Medicine, Treatment and Management of Anal Cancer, Surgery, Tumor Microenvironment, Cancer Immunoediting, Biomarkers for Immunotherapy, Immunotherapy, Immune system, Tumor microenvironment, FOXP3, Immune checkpoint, Cancer research, Immunology, FOS Clinical medicine, Internal medicine

الوصف: Lung adenosquamous carcinoma (ASC) is an uncommon histological subtype. We aimed to characterize the tumor immune microenvironment (TIME) in lung ASC and estimate patient response to immune checkpoint inhibitors (ICIs), which have never been systematically investigated. In cohort I, we collected 30 ASCs from a single center for analysis of TIME characteristics, including immuno-phenotyping, tumor mutation burden (TMB), T-cell receptor (TCR) repertoires, tumor-infiltrating lymphocytes (TILs), and immune checkpoint expression. Twenty-two (73.3%) patients were EGFR-positive. The TIME was defined by immune-excluded (60%) and immune-desert phenotype (40%). Strikingly, programmed cell death-ligand 1 (PD-L1) and programmed cell death-1 (PD-1) were predominantly expressed in squamous cell carcinoma components (SCCCs) versus adenocarcinoma components (ACCs), where enhanced CD4+ FOXP3+ regulatory T cell and attenuated CD57+ natural killer cell infiltration were present, consistent with a landscape of fewer innate ... : سرطان الرئة الغدي الصدفي (ASC) هو نوع فرعي نسيجي غير شائع. كنا نهدف إلى توصيف البيئة الدقيقة المناعية للورم (TIME) في ASC الرئة وتقدير استجابة المريض لمثبطات نقاط التفتيش المناعية (ICIs)، والتي لم يتم التحقيق فيها بشكل منهجي. في المجموعة الأولى، جمعنا 30 ASCs من مركز واحد لتحليل خصائص الوقت، بما في ذلك التنميط الظاهري المناعي، وعبء طفرة الورم (TMB)، ومرجع مستقبلات الخلايا التائية (TCR)، والخلايا الليمفاوية المتسللة للورم (TILs)، والتعبير المناعي عن نقطة التفتيش. كان اثنان وعشرون (73.3 ٪) مريضًا مصابًا بـ EGFR. تم تحديد الوقت من خلال النمط الظاهري المناعي المستبعد (60 ٪) والنمط الظاهري المناعي الصحراوي (40 ٪). ومن اللافت للنظر أنه تم التعبير عن موت الخلايا المبرمج 1 (PD - L1) وموت الخلايا المبرمج 1 (PD -1) في الغالب في مكونات سرطان الخلايا الحرشفية (SCCCs) مقابل مكونات السرطان الغدي (ACCS)، حيث كانت الخلايا التائية التنظيمية المعززة CD4 + FOXP3 + والخلايا التائية الموهنة CD57 + تسلل الخلايا القاتلة الطبيعية موجودة، بما يتفق مع مشهد من عدد أقل من الخلايا المناعية الفطرية، وخلايا أكثر تثبيطًا للمناعة. كان لدى ...

العلاقة: https://dx.doi.org/10.60692/baj7t-t9049Test

الإتاحة: https://doi.org/10.60692/yx21j-v715110.60692/baj7t-t9049Test

المؤلفون: Xinlong Zheng, Tao Lu, Kan Jiang, Chao Li, Qian Miao, Longfeng Zhang, Xiaobin Zheng, Shanshan Yang, Weijin Xiao, Gen Lin, Mingqiu Chen

المصدر: Cancer Management and Research

مصطلحات موضوعية: immune-checkpoint inhibitor, medicine.medical_specialty, Predictive marker, Necrosis, Combination therapy, business.industry, Proportional hazards model, medicine.medical_treatment, ECOG Performance Status, cavity, Immunotherapy, Gastroenterology, necrosis, Oncology, Cancer Management and Research, Internal medicine, lung squamous cell carcinoma, Medicine, Tumor necrosis factor alpha, Risk factor, medicine.symptom, business, predictive marker, Original Research

الوصف: Tao Lu,1,* Longfeng Zhang,2,* Mingqiu Chen,3 Xiaobin Zheng,2 Kan Jiang,2 Xinlong Zheng,2 Chao Li,4 Weijin Xiao,4 Qian Miao,2 Shanshan Yang,2 Gen Lin2 1Department of Radiology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 2Department of Thoracic Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 3Department of Thoracic Radiation Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China; 4Department of Pathology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of China*These authors contributed equally to this workCorrespondence: Gen LinDepartment of Thoracic Oncology, Fujian Medical University Cancer Hospital, Fujian Cancer Hospital, Fuzhou, People’s Republic of ChinaEmail fjzllg133@fjzlhospital.comBackground: Predictive markers for guidance and monitoring of immunotherapy in lung squamous cell carcinoma (LSCC) are an interesting topic but have yet to be fully explored. A primary characteristic of LSCC is tumor necrosis that results in extensive immune suppression in patients. We sought to assess whether tumor necrosis or cavity on baseline CT could effectively predict the efficacy of immune checkpoint inhibitors (ICIs) in advanced LSCC.Methods: Advanced LSCC cases undergoing pre-treatment chest CT imaging and receiving ICIs were retrospectively collected. All CT images were reviewed by an independent chest radiologist blinded to any previous diagnosis to confirm morphological alterations in necrosis or cavity. We performed Logistic regression and developed Cox proportional hazards models to assess the predictive performance of baseline necrosis or cavity characteristics in advanced LSCC. Survival estimates were observed using Kaplan–Meier curves.Results: Ninety-three patients were eligible for analysis, predominantly consisting of patients with ECOG performance status of 0 or 1 (97.8%), male patients (95.7%), and heavy smokers (92.5%). Intrapulmonic necrosis or cavity on CT scan was present in 52.7% of all patients. Generally, the objective response rate (ORR) in patients with necrosis or cavity to ICI treatment was significantly worse versus those without (30.6% vs 54.5%, p = 0.020), with the subgroup ORRs as follows: ICI monotherapy (necrosis vs non-necrosis: 10.0% vs 36.8%, p =0.047) and ICI combination therapy (44.8% vs 68.0%, p =0.088). Multivariable analysis identified intrapulmonic necrosis or cavity at baseline as a major risk factor for advanced LSCC (HR 4.042, 95% CI1.149– 10.908, p = 0.006). Multivariate Cox analysis showed that baseline necrosis or cavity and ICI monotherapy were unfavorable factors for progression-free survival (HR 1.729; 95% CI1.203– 2.484, p =0.003).Conclusion: LSCC patients with intrapulmonic cavity or necrosis on baseline CT scan may respond poorly to anti-PD-(L)1-treatment, monotherapy and combination therapy alike.Keywords: lung squamous cell carcinoma, immune-checkpoint inhibitor, predictive marker, necrosis, cavity

وصف الملف: text/html

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::891247be1ccccdc07905feb5ececbf41Test
https://doi.org/10.2147/cmar.s319480Test

المؤلفون: Xinlong, Zheng, Kan, Jiang, Weijin, Xiao, Dongqiang, Zeng, Wenying, Peng, Jing, Bai, Xiaohui, Chen, Pansong, Li, Longfeng, Zhang, Xiaobin, Zheng, Qian, Miao, Haibo, Wang, Shiwen, Wu, Yiquan, Xu, Haipeng, Xu, Chao, Li, Lifeng, Li, Xuan, Gao, Suya, Zheng, Junhui, Li, Deqiang, Wang, Zhipeng, Zhou, Xuefeng, Xia, Shanshan, Yang, Yujing, Li, Zhaolei, Cui, Qiuyu, Zhang, Ling, Chen, Xiandong, Lin, Gen, Lin

المصدر: Frontiers in immunology. 13

مصطلحات موضوعية: Lung Neoplasms, Cancer-Associated Fibroblasts, Predictive Value of Tests, Biomarkers, Tumor, Tumor Microenvironment, Humans, Immunologic Factors, Immunotherapy, CD8-Positive T-Lymphocytes, Prognosis, B7-H1 Antigen

الوصف: Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) are critical for immune suppression by restricting immune cell infiltration in the tumor stromal zones from penetrating tumor islands and changing their function status, particularly for CD8The TME was characterized using immunohistochemical (IHC) analysis using a large-scale sample size of gene expression profiles. The CD8Compared with normal tissue, CAFs were enriched in cancer tissue, and the amount of CAFs was overwhelmingly higher than that in other immune cells. CAFs are positively correlated with the extent of immune infiltration. A higher CFR was strongly associated with improved survival in lung cancer, melanoma, and urothelial cancer immunotherapy cohorts. Within most cohorts, there was no clear evidence for an association between CFR and programmed death-ligand 1 (PD-L1) or tumor mutational burden (TMB). Compared with TMB and PD-L1, a higher correlation coefficient was observed between CFR and the ORR following pembrolizumab monotherapy in 20 solid tumor types (Spearman's r = 0.69CFR is a newly found and simple parameter that can be used for identifying patients unlikely to benefit from immunotherapy. Future studies are needed to confirm this finding.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=pmid________::11444db804d1af27ed814917f68b5c45Test
https://pubmed.ncbi.nlm.nih.gov/36439099Test

المؤلفون: Biao Wu, Longfeng Zhang, Qian Miao, Xiaobin Zheng, Gen Lin, Kan Jiang

المصدر: Annals of Palliative Medicine. 10:4982-4986

مصطلحات موضوعية: Male, 0301 basic medicine, Oncology, medicine.medical_specialty, Lung Neoplasms, medicine.medical_treatment, Population, non-small cell lung cancer (NSCLC), B7-H1 Antigen, 03 medical and health sciences, 0302 clinical medicine, Carcinoma, Non-Small-Cell Lung, Internal medicine, Tumor Microenvironment, medicine, Humans, Lung cancer, education, Advanced and Specialized Nursing, Tumor microenvironment, education.field_of_study, business.industry, Combination chemotherapy, Chemoradiotherapy, Immunotherapy, Middle Aged, medicine.disease, Radiation therapy, 030104 developmental biology, Anesthesiology and Pain Medicine, 030220 oncology & carcinogenesis, Mutation, business

الوصف: Immune checkpoint inhibitors (ICIs) have become an important milestone in the treatment of non-small cell lung cancer (NSCLC). High expression of protein ligand 1 (PD-L1) and tumor mutation burden (TMB) can help to select the dominant population for immunotherapy, but the expression of PD-L1 does not seem to be unchanged. A 61-year-old man with adenocarcinoma of the lung experienced postoperative recurrence. PD-L1 expression was negative before recurrence, and TMB was stable by next-generation sequencing (NGS) test. However, after radiotherapy and chemotherapy, PD-L1 positive expression was found in a re-biopsy specimen, and NGS detection indicated the loss of immune negative predictive genes. The patient achieved a durable response to a posterior-line immunotherapy combined chemotherapy. The tumor microenvironment maybe changed after chemoradiotherapy, which provides an opportunity for patients to benefit from immunotherapy. The use of NGS in dynamic detection and PD-L1 expression may help monitor this change in the tumor microenvironment, the transition from cold to hot tumor. This case maybe provides new clinical evidence that a non-immuno-dominant population in the initial state can be converted to a population with the benefit of immunotherapy after chemoradiotherapy. However, patients who are initially unsuitable for immunotherapy may still need to undergo combined immunotherapy to achieve a clinical benefit.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_dedup___::2aa0135a87fb293551dfe4a6e4aa210eTest
https://doi.org/10.21037/apm-21-761Test

المؤلفون: Xinlong Zheng, Kan Jiang, Weijin Xiao, Dongqiang Zeng, Wenying Peng, Jing Bai, Xiaohui Chen, Pansong Li, Longfeng Zhang, Xiaobin Zheng, Qian Miao, Haibo Wang, Shiwen Wu, Yiquan Xu, Haipeng Xu, Chao Li, Lifeng Li, Xuan Gao, Suya Zheng, Junhui Li

المصدر: Frontiers in Immunology; 11/9/2022, Vol. 13, p01-16, 16p

مصطلحات موضوعية: FIBROBLASTS, GENE expression profiling, IMMUNOTHERAPY, T cells, IMMUNOSUPPRESSION

مستخلص: Background: Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) are critical for immune suppression by restricting immune cell infiltration in the tumor stromal zones from penetrating tumor islands and changing their function status, particularly for CD8⁺ T cells. However, assessing and quantifying the impact of CAFs on immune cells and investigating how this impact is related to clinical outcomes, especially the efficacy of immunotherapy, remain unclear. Materials and methods: The TME was characterized using immunohistochemical (IHC) analysis using a large-scale sample size of gene expression profiles. The CD8⁺ T cell/CAF ratio (CFR) association with survival was investigated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) lung cancer cohorts. The correlation between CFR and immunotherapeutic efficacy was computed in five independent cohorts. The correlation between CFR and objective response rates (ORRs) following pembrolizumab monotherapy was investigated in 20 solid tumor types. To facilitate clinical translation, the IHC-detected CD8/α-SMA ratio was applied as an immunotherapeutic predictive biomarker in a real-world lung cancer cohort. Results: Compared with normal tissue, CAFs were enriched in cancer tissue, and the amount of CAFs was overwhelmingly higher than that in other immune cells. CAFs are positively correlated with the extent of immune infiltration. A higher CFR was strongly associated with improved survival in lung cancer, melanoma, and urothelial cancer immunotherapy cohorts. Within most cohorts, there was no clear evidence for an association between CFR and programmed death-ligand 1 (PD-L1) or tumor mutational burden (TMB). Compared with TMB and PD-L1, a higher correlation coefficient was observed between CFR and the ORR following pembrolizumab monotherapy in 20 solid tumor types (Spearman's r = 0.69 vs. 0.44 and 0.21). In a real-world cohort, patients with a high CFR detected by IHC benefited considerably from immunotherapy as compared with those with a low CFR (hazard ratio, 0.37; 95% confidence interval, 0.19-0.75; p < 0.001). Conclusions: CFR is a newly found and simple parameter that can be used for identifying patients unlikely to benefit from immunotherapy. Future studies are needed to confirm this finding. [ABSTRACT FROM AUTHOR]

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المؤلفون: Xinlong Zheng, Kan Jiang, Weijin Xiao, Dongqiang Zeng, Wenying Peng, Jing Bai, Xiaohui Chen, Pansong Li, Longfeng Zhang, Xiaobin Zheng, Qian Miao, Haibo Wang, Shiwen Wu, Yiquan Xu, Haipeng Xu, Chao Li, Lifeng Li, Xuan Gao, Suya Zheng, Junhui Li, Deqiang Wang, Zhipeng Zhou, Xuefeng Xia, Shanshan Yang, Yujing Li, Zhaolei Cui, Qiuyu Zhang, Ling Chen, Xiandong Lin, Gen Lin

مصطلحات موضوعية: Immunology, Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies), Autoimmunity, Cellular Immunology, Humoural Immunology and Immunochemistry, Immunogenetics (incl. Genetic Immunology), Innate Immunity, Transplantation Immunology, Tumour Immunology, Immunology not elsewhere classified, Genetic Immunology, Animal Immunology, Veterinary Immunology, CD8+ T cell, cancer-associated fibroblast, prognostic biomarker, predictive biomarker, immunotherapy

الوصف: Background Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) are critical for immune suppression by restricting immune cell infiltration in the tumor stromal zones from penetrating tumor islands and changing their function status, particularly for CD8 + T cells. However, assessing and quantifying the impact of CAFs on immune cells and investigating how this impact is related to clinical outcomes, especially the efficacy of immunotherapy, remain unclear. Materials and methods The TME was characterized using immunohistochemical (IHC) analysis using a large-scale sample size of gene expression profiles. The CD8 + T cell/CAF ratio (CFR) association with survival was investigated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) lung cancer cohorts. The correlation between CFR and immunotherapeutic efficacy was computed in five independent cohorts. The correlation between CFR and objective response rates (ORRs) following pembrolizumab monotherapy was investigated in 20 solid tumor types. To facilitate clinical translation, the IHC-detected CD8/α-SMA ratio was applied as an immunotherapeutic predictive biomarker in a real-world lung cancer cohort. Results Compared with normal tissue, CAFs were enriched in cancer tissue, and the amount of CAFs was overwhelmingly higher than that in other immune cells. CAFs are positively correlated with the extent of immune infiltration. A higher CFR was strongly associated with improved survival in lung cancer, melanoma, and urothelial cancer immunotherapy cohorts. Within most cohorts, there was no clear evidence for an association between CFR and programmed death-ligand 1 (PD-L1) or tumor mutational burden (TMB). Compared with TMB and PD-L1, a higher correlation coefficient was observed between CFR and the ORR following pembrolizumab monotherapy in 20 solid tumor types (Spearman’s r = 0.69 vs. 0.44 and 0.21). In a real-world cohort, patients with a high CFR detected by IHC benefited considerably from immunotherapy as compared with those ...

العلاقة: https://figshare.com/articles/dataset/DataSheet_2_CD8_T_cell_cancer-associated_fibroblast_ratio_stratifies_prognostic_and_predictive_responses_to_immunotherapy_across_multiple_cancer_types_pdf/21523203Test

الإتاحة: https://doi.org/10.3389/fimmu.2022.974265.s002Test
https://figshare.com/articles/dataset/DataSheet_2_CD8_T_cell_cancer-associated_fibroblast_ratio_stratifies_prognostic_and_predictive_responses_to_immunotherapy_across_multiple_cancer_types_pdf/21523203Test

المؤلفون: Xinlong Zheng, Kan Jiang, Weijin Xiao, Dongqiang Zeng, Wenying Peng, Jing Bai, Xiaohui Chen, Pansong Li, Longfeng Zhang, Xiaobin Zheng, Qian Miao, Haibo Wang, Shiwen Wu, Yiquan Xu, Haipeng Xu, Chao Li, Lifeng Li, Xuan Gao, Suya Zheng, Junhui Li, Deqiang Wang, Zhipeng Zhou, Xuefeng Xia, Shanshan Yang, Yujing Li, Zhaolei Cui, Qiuyu Zhang, Ling Chen, Xiandong Lin, Gen Lin

مصطلحات موضوعية: Immunology, Applied Immunology (incl. Antibody Engineering, Xenotransplantation and T-cell Therapies), Autoimmunity, Cellular Immunology, Humoural Immunology and Immunochemistry, Immunogenetics (incl. Genetic Immunology), Innate Immunity, Transplantation Immunology, Tumour Immunology, Immunology not elsewhere classified, Genetic Immunology, Animal Immunology, Veterinary Immunology, CD8+ T cell, cancer-associated fibroblast, prognostic biomarker, predictive biomarker, immunotherapy

الوصف: Background Cancer-associated fibroblasts (CAFs) within the tumor microenvironment (TME) are critical for immune suppression by restricting immune cell infiltration in the tumor stromal zones from penetrating tumor islands and changing their function status, particularly for CD8 + T cells. However, assessing and quantifying the impact of CAFs on immune cells and investigating how this impact is related to clinical outcomes, especially the efficacy of immunotherapy, remain unclear. Materials and methods The TME was characterized using immunohistochemical (IHC) analysis using a large-scale sample size of gene expression profiles. The CD8 + T cell/CAF ratio (CFR) association with survival was investigated in The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) lung cancer cohorts. The correlation between CFR and immunotherapeutic efficacy was computed in five independent cohorts. The correlation between CFR and objective response rates (ORRs) following pembrolizumab monotherapy was investigated in 20 solid tumor types. To facilitate clinical translation, the IHC-detected CD8/α-SMA ratio was applied as an immunotherapeutic predictive biomarker in a real-world lung cancer cohort. Results Compared with normal tissue, CAFs were enriched in cancer tissue, and the amount of CAFs was overwhelmingly higher than that in other immune cells. CAFs are positively correlated with the extent of immune infiltration. A higher CFR was strongly associated with improved survival in lung cancer, melanoma, and urothelial cancer immunotherapy cohorts. Within most cohorts, there was no clear evidence for an association between CFR and programmed death-ligand 1 (PD-L1) or tumor mutational burden (TMB). Compared with TMB and PD-L1, a higher correlation coefficient was observed between CFR and the ORR following pembrolizumab monotherapy in 20 solid tumor types (Spearman’s r = 0.69 vs. 0.44 and 0.21). In a real-world cohort, patients with a high CFR detected by IHC benefited considerably from immunotherapy as compared with those ...

العلاقة: https://figshare.com/articles/dataset/Table_1_CD8_T_cell_cancer-associated_fibroblast_ratio_stratifies_prognostic_and_predictive_responses_to_immunotherapy_across_multiple_cancer_types_xls/21523206Test

الإتاحة: https://doi.org/10.3389/fimmu.2022.974265.s003Test
https://figshare.com/articles/dataset/Table_1_CD8_T_cell_cancer-associated_fibroblast_ratio_stratifies_prognostic_and_predictive_responses_to_immunotherapy_across_multiple_cancer_types_xls/21523206Test

المؤلفون: Deqiang Wang, Dongqiang Zeng, Kan Jiang, Chao Li, Zhipeng Zhou, Qian Miao, Jing Bai, Feng Long, Junhui Li, Lifeng Li, Lin Gen, Biao Wu, Xuan Gao, Wenying Peng, Yi Yin, Xinlong Zheng, Pansong Li, Jianming Ding, Haipeng Xu, Suya Zheng

المصدر: Journal of Clinical Oncology. 38:9536-9536

مصطلحات موضوعية: Cancer Research, Tumor microenvironment, business.industry, medicine.medical_treatment, Immunotherapy, medicine.disease, 03 medical and health sciences, 0302 clinical medicine, Oncology, Tumor progression, 030220 oncology & carcinogenesis, Cancer research, Medicine, Cytotoxic T cell, Non small cell, business, Lung cancer, 030215 immunology

الوصف: 9536 Background: Cancer-related fibroblasts (CAFs) are important components of the tumor microenvironment (TME) and play a key role in tumor progression. There is growing evidence that CAF levels in tumors are highly correlated with treatment response and prognosis. However, the effect of CAFs on immunotherapy response remains unknown. Methods: RNA-seq and clinical data were downloaded from TCGA and GEO. The SVA package ComBat function was used to remove batch effects. The ssGSEA algorithm was used to assess the level of cell infiltration in each sample. OS (overall survival) and DFS (disease free survival) were analyzed using the Kaplan–Meier method. GO enrichment analysis was used to assess the biological processes of subgroup differential genes. The Tumor Immune Dysfunction and Exclusion (TIDE) algorithm and subclass mapping were used to predict the clinical response to immune checkpoint blockade. Results: We evaluated the infiltration abundance of 24 types of immune cells and fibroblasts in 1768 NSCLC samples and found that almost all IMFRs (immune cells / fibroblasts) are beneficial to the prognosis. This phenomenon is called “CAFs-mediated immune resistance pattern (CMIRP)”. We evaluated the infiltration abundance of 24 types of immune cells and fibroblasts in 1768 NSCLC samples and found that almost all IMFRs (immune cells / fibroblasts) are beneficial to the prognosis. This phenomenon is called “CAFs-mediated immune resistance pattern (CMIRP)”. The prognosis according to CD8+ T cells was not strong, but CD8+ T cells / fibroblasts (CFR) were significant protective prognostic factors [n = 1588; hazard ratio (HR), 0.66; 95% confidence interval (CI), 0.56–0.78; P < 0.001]. Multivariate analysis revealed that the CFR was an independent prognostic biomarker. The TCGA pan-cancer cohort confirmed the widespread presence of CMIRP in cancer. We further defined the CFR high and CFR low subgroups. CFR high samples were enriched with immune activation pathways including T cell activation, cytolysis, and antigen presentation, while CFR low was associated with immunosuppression including activation of transforming growth factor β, epithelial-mesenchymal transition, and angiogenesis pathways. Finally, we combined TIDE and submap to speculate that CFR is a potential prognostic marker of immunotherapy for NSCLC. Conclusions: We proposed the term “CMIRP” to shed light on a more accurate assessment of immune status. CFR is a potential marker for prognosis and predictive efficacy of immunotherapy in NSCLC.

الوصول الحر: https://explore.openaire.eu/search/publication?articleId=doi_________::b766cffa3bea1e8986205902855b9ebdTest
https://doi.org/10.1200/jco.2020.38.15_suppl.9536Test