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推进胰腺癌免疫治疗:新兴过继细胞疗法简要综述

英文原题:Advancing Immunotherapy in Pancreatic Cancer: A Brief Review of Emerging Adoptive Cell Therapies.

PubMed 2025/02/09(内容时间) Cancers (Basel) Q2 · IF 4.8(JCR 2025)

研究概要

胰腺癌在主要癌症中5年生存率最低(13%),是美国癌症相关死亡的第三大原因。

中文摘要

胰腺癌在主要癌症中5年生存率最低(13%),是美国癌症相关死亡的第三大原因。这种癌症的高致死率归因于其起病隐匿、诊断时多为晚期、进展迅速以及治疗选择有限。应对这些挑战需要更深入地了解复杂的肿瘤微环境,以确定新的治疗靶点。过继性细胞疗法等较新的方法在治疗血液系统恶性肿瘤方面已取得显著成功,但其在实体瘤尤其是胰腺癌中的应用仍处于早期开发阶段。ACT广泛涉及从患者体内分离免疫细胞(T淋巴细胞、NK 细胞和巨噬细胞),随后通过基因工程增强并建立特异性抗肿瘤反应。目前有多种ACT模式正在胰腺癌中进行研究,包括CAR-T 细胞、嵌合抗原受体NK细胞(CAR-NK)、TIL(肿瘤浸润淋巴细胞)、T细胞受体(TCR)工程化T细胞以及细胞因子诱导的杀伤细胞(CIK)。主要障碍一直是识别可操作的肿瘤抗原,并递送聚焦的细胞疗法以克服胰腺癌周围免疫抑制性和致密纤维化间质。需要进一步研究以探索细胞疗法在胰腺癌中面临的局限性,并确定新的联合治疗方法,从而改善临床结局。

展开英文摘要原文

Pancreatic cancer has the lowest 5-year survival rate (13%) among major cancers and is the third leading cause of cancer-related deaths in the United States. The high lethality of this cancer is attributed to its insidious onset, late-stage diagnosis, rapid progression, and limited treatment options. Addressing these challenges requires a deeper understanding of the complex tumor microenvironment to identify novel therapeutic targets. Newer approaches like adoptive cell therapy have shown remarkable success in treating hematological malignancies, but their application in solid tumors, particularly pancreatic cancer, is still in the early stages of development. ACT broadly involves isolating immune cells (T lymphocytes, Natural Killer cells, and macrophages) from the patient, followed by genetic engineering to enhance and mount a specific anti-tumor response. Various ACT modalities are under investigation for pancreatic cancer, including chimeric antigen receptor T cells (CAR-T), chimeric antigen receptor NK cells (CAR-NK), tumor-infiltrating lymphocytes (TIL), T-cell receptor (TCR)-engineered T cells, and cytokine-induced killer cells (CIK). Major hurdles have been identifying actionable tumor antigens and delivering focused cellular therapies to overcome the immunosuppressive and dense fibrotic stroma surrounding the pancreatic cancer. Further studies are needed to explore the limitations faced by cellular therapy in pancreatic cancer and identify novel combination treatment approaches in order to improve clinical outcomes.

论文信息

作者
Sherpally D、Manne A
第一作者单位
Department of Internal Medicine, New York Medical College, Metropolitan, New York, NY 10029, USA.United States
通讯作者单位
Department of Internal Medicine, Division of Medical Oncology, The Arthur G. James Cancer Hospital and Richard J. Solove Research Institute, The Ohio State University Comprehensive Cancer Center, Columbus, OH 43210, USA.United States
文献类型
综述
期刊
Cancers2025 Feb 9
原文标识
PubMed 40002184 · DOI 10.3390/cancers17040589