决定异体 CAR T 细胞排斥与扩增的细胞和分子机制
Cellular and molecular mechanisms determining allogeneic CAR T cell rejection and expansion.
我们评估了11例接受单一批次cemacabtagene ansegedleucel(cema-cel)治疗的大B细胞淋巴瘤患者,cemacabtagene ansegedleucel是一种异体抗CD19 CAR T产品。
英文原题:Tumor-Immune Interactions in Pediatric Oral Rhabdomyosarcoma: A Narrative Review on Immuno-Oncology and Emerging Therapies.
儿童口腔横纹肌肉瘤(RMS)是一种罕见且侵袭性强的头颈部肿瘤,其特征为复杂且以免疫抑制为主的肿瘤免疫微环境。
儿童口腔横纹肌肉瘤(RMS)是一种罕见且侵袭性强的头颈部癌症,其肿瘤免疫微环境复杂且多呈免疫抑制状态。与成人癌症不同,儿童RMS通常呈“免疫冷”特征,包括T细胞浸润极少、突变负荷低以及对免疫检查点阻断耐药。肿瘤位于口腔还会因解剖和功能限制增加治疗难度。此外,PAX3:FOXO1等融合癌基因可通过破坏抗原呈递、减少免疫细胞浸润而降低免疫原性和治疗应答。肿瘤免疫学进展带来了免疫检查点抑制剂、嵌合抗原受体(CAR)疗法、癌症疫苗和溶瘤病毒等新策略。然而,由于儿童免疫系统发育特点,这些方法在儿童人群中面临特定挑战。本叙述性综述介绍儿童口腔RMS免疫生物学的近期发现,重点讨论肿瘤-免疫相互作用及其对疾病进展和治疗耐药的影响。综述分析肿瘤免疫微环境的细胞组分、免疫逃逸机制以及PD-L1和B7-H3等免疫检查点的表达,并讨论新兴免疫疗法,包括CAR-T、CAR-NK、CAR-CIK细胞疗法、检查点抑制剂、溶瘤病毒和癌症疫苗,重点阐述其当前局限及重塑儿童RMS免疫微环境的潜力。
Pediatric oral rhabdomyosarcoma (RMS) is a rare and aggressive cancer of the head and neck, characterized by a complex and mostly immunosuppressive tumor-immune microenvironment. Unlike adult cancers, pediatric RMS typically exhibits a "cold" immune profile, characterized by minimal T-cell infiltration, a low mutational burden, and resistance to immune checkpoint blockade. The tumor's location in the oral cavity adds difficulty to treatment because of anatomical and functional limitations. Additionally, the presence of fusion oncogenes, such as PAX3:FOXO1, hampers immunogenicity and treatment response by disrupting antigen presentation and reducing immune cell infiltration. Advances in immuno-oncology have introduced new strategies, including immune checkpoint inhibitors, chimeric antigen receptor (CAR) therapies, cancer vaccines, and oncolytic viruses. However, these approaches face specific challenges in the pediatric population due to developmental immune factors. This narrative review highlights recent findings on the immunobiology of pediatric oral RMS, focusing on tumor-immune interactions and their impact on disease progression and treatment resistance. We reviewed the cellular components of the TIME, the mechanisms of immune evasion, and the expression of immune checkpoints, including PD-L1 and B7-H3. Emerging immunotherapies, including CAR-T, CAR-NK, and CAR-CIK cell therapies; checkpoint inhibitors; oncolytic viruses; and cancer vaccines, are discussed, with an emphasis on their current limitations and potential to transform the pediatric RMS immune landscape.
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