Enrico Sammarco, Martina Rossetti, Alessia Salfi, Adele Bonato, Paolo Viacava, Gianluca Masi, Luca Galli, Pinuccia Faviana
{"title":"肿瘤微环境与转移性肾细胞癌一线免疫疗法组合的临床疗效。","authors":"Enrico Sammarco, Martina Rossetti, Alessia Salfi, Adele Bonato, Paolo Viacava, Gianluca Masi, Luca Galli, Pinuccia Faviana","doi":"10.1007/s12032-024-02370-0","DOIUrl":null,"url":null,"abstract":"<p><p>The impact of tumor microenvironment (TME) in influencing clinical response to first-line immune checkpoint inhibitor (ICI)-based treatment in advanced renal cell carcinoma (RCC) is unclear. Immunohistochemistry (IHC) could identify biomarkers related to immune checkpoints and immune cell population. This study retrospectively characterized TME from 28 RCC patients who received first line ICI-based therapy through IHC assessment of selected markers and explored preliminary evidence about their possible correlation with treatment efficacy. We found a significantly higher count of CD80+, CD163+ cells and their ratio in RCC with clear cell component compared to those without clear cell features; additionally, patients with metastatic disease at diagnosis were associated with higher expression of CD163+ cells, while higher count of CD4+ cells and CD4+/CD8+ ratio were found in RCC with sarcomatoid features. Patients achieving partial or complete response were associated with lower expression of CD163+ cells (median 28 vs 47; p = 0.049). Furthermore, lower expression of CD163+ was associated with better PFS (median PFS 20.0 vs 4.7 months; HR 0.22 p = 0.011) and OS (median OS NR vs 14.4 months; HR 0.28 p = 0.036). A longer OS was reported in PD-L1 CPS negative patients (median OS NR vs 11.8 months; HR 0.20 p = 0.024). High infiltration of CD163+ macrophages, who typically present \"anti-inflammatory\" M2-like phenotype, could identify a subgroup of patients with poor survival after receiving first-line ICI.</p>","PeriodicalId":18433,"journal":{"name":"Medical Oncology","volume":null,"pages":null},"PeriodicalIF":2.8000,"publicationDate":"2024-05-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090963/pdf/","citationCount":"0","resultStr":"{\"title\":\"Tumor microenvironment and clinical efficacy of first line immunotherapy-based combinations in metastatic renal cell carcinoma.\",\"authors\":\"Enrico Sammarco, Martina Rossetti, Alessia Salfi, Adele Bonato, Paolo Viacava, Gianluca Masi, Luca Galli, Pinuccia Faviana\",\"doi\":\"10.1007/s12032-024-02370-0\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p>The impact of tumor microenvironment (TME) in influencing clinical response to first-line immune checkpoint inhibitor (ICI)-based treatment in advanced renal cell carcinoma (RCC) is unclear. Immunohistochemistry (IHC) could identify biomarkers related to immune checkpoints and immune cell population. This study retrospectively characterized TME from 28 RCC patients who received first line ICI-based therapy through IHC assessment of selected markers and explored preliminary evidence about their possible correlation with treatment efficacy. We found a significantly higher count of CD80+, CD163+ cells and their ratio in RCC with clear cell component compared to those without clear cell features; additionally, patients with metastatic disease at diagnosis were associated with higher expression of CD163+ cells, while higher count of CD4+ cells and CD4+/CD8+ ratio were found in RCC with sarcomatoid features. Patients achieving partial or complete response were associated with lower expression of CD163+ cells (median 28 vs 47; p = 0.049). Furthermore, lower expression of CD163+ was associated with better PFS (median PFS 20.0 vs 4.7 months; HR 0.22 p = 0.011) and OS (median OS NR vs 14.4 months; HR 0.28 p = 0.036). A longer OS was reported in PD-L1 CPS negative patients (median OS NR vs 11.8 months; HR 0.20 p = 0.024). High infiltration of CD163+ macrophages, who typically present \\\"anti-inflammatory\\\" M2-like phenotype, could identify a subgroup of patients with poor survival after receiving first-line ICI.</p>\",\"PeriodicalId\":18433,\"journal\":{\"name\":\"Medical Oncology\",\"volume\":null,\"pages\":null},\"PeriodicalIF\":2.8000,\"publicationDate\":\"2024-05-13\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11090963/pdf/\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Medical Oncology\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1007/s12032-024-02370-0\",\"RegionNum\":4,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q2\",\"JCRName\":\"ONCOLOGY\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Medical Oncology","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1007/s12032-024-02370-0","RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q2","JCRName":"ONCOLOGY","Score":null,"Total":0}
引用次数: 0
摘要
肿瘤微环境(TME)对晚期肾细胞癌(RCC)一线免疫检查点抑制剂(ICI)治疗临床反应的影响尚不明确。免疫组化(IHC)可以确定与免疫检查点和免疫细胞群相关的生物标记物。本研究通过对选定标记物进行IHC评估,对28例接受一线ICI治疗的RCC患者的TME进行了回顾性特征描述,并探讨了这些标记物与治疗效果之间可能存在的相关性的初步证据。我们发现,与无透明细胞特征的患者相比,有透明细胞成分的RCC患者中CD80+、CD163+细胞的数量及其比值明显更高;此外,诊断时患有转移性疾病的患者与CD163+细胞的高表达相关,而有肉瘤特征的RCC患者中CD4+细胞的数量和CD4+/CD8+比值更高。获得部分或完全应答的患者 CD163+ 细胞表达量较低(中位数为 28 vs 47;p = 0.049)。此外,较低的 CD163+ 表达与较好的 PFS(中位 PFS 20.0 个月 vs 4.7 个月;HR 0.22 p = 0.011)和 OS(中位 OS NR vs 14.4 个月;HR 0.28 p = 0.036)相关。PD-L1 CPS阴性患者的OS更长(中位OS NR vs 11.8个月;HR 0.20 p = 0.024)。CD163+ 巨噬细胞的高浸润率通常表现为 "抗炎 "的 M2 样表型,可识别出接受一线 ICI 后生存率较低的患者亚群。
Tumor microenvironment and clinical efficacy of first line immunotherapy-based combinations in metastatic renal cell carcinoma.
The impact of tumor microenvironment (TME) in influencing clinical response to first-line immune checkpoint inhibitor (ICI)-based treatment in advanced renal cell carcinoma (RCC) is unclear. Immunohistochemistry (IHC) could identify biomarkers related to immune checkpoints and immune cell population. This study retrospectively characterized TME from 28 RCC patients who received first line ICI-based therapy through IHC assessment of selected markers and explored preliminary evidence about their possible correlation with treatment efficacy. We found a significantly higher count of CD80+, CD163+ cells and their ratio in RCC with clear cell component compared to those without clear cell features; additionally, patients with metastatic disease at diagnosis were associated with higher expression of CD163+ cells, while higher count of CD4+ cells and CD4+/CD8+ ratio were found in RCC with sarcomatoid features. Patients achieving partial or complete response were associated with lower expression of CD163+ cells (median 28 vs 47; p = 0.049). Furthermore, lower expression of CD163+ was associated with better PFS (median PFS 20.0 vs 4.7 months; HR 0.22 p = 0.011) and OS (median OS NR vs 14.4 months; HR 0.28 p = 0.036). A longer OS was reported in PD-L1 CPS negative patients (median OS NR vs 11.8 months; HR 0.20 p = 0.024). High infiltration of CD163+ macrophages, who typically present "anti-inflammatory" M2-like phenotype, could identify a subgroup of patients with poor survival after receiving first-line ICI.
期刊介绍:
Medical Oncology (MO) communicates the results of clinical and experimental research in oncology and hematology, particularly experimental therapeutics within the fields of immunotherapy and chemotherapy. It also provides state-of-the-art reviews on clinical and experimental therapies. Topics covered include immunobiology, pathogenesis, and treatment of malignant tumors.