免疫检查点阻断通过扩增效应 CD8⁺ T 细胞克隆增强淋巴细胞清除性化疗诱导的抗肿瘤免疫
Immune Checkpoint Blockade Augments Lymphodepleting Chemotherapy-Induced Antitumor Immunity by Expanding Effector CD8+ T-cell Clones.
CELL INTELLIGENCE · 肿瘤细胞治疗研究
肿瘤细胞治疗研究
英文原题:Tumor-infiltrating lymphocytes for adoptive cell therapy: recent advances, challenges, and future directions.
Tumor-infiltrating lymphocytes for adoptive cell therapy: recent advances, challenges, and future directions.
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目前有许多正在进行的研究领域,聚焦于提高临床疗效和优化基于 TIL 的 ACT。
引言:利用TIL(肿瘤浸润淋巴细胞)的过继细胞治疗(ACT)是一种高度个体化的癌症免疫疗法,利用来源于患者肿瘤的天然TIL。该治疗已在黑色素瘤中显示稳定的临床应答,近期结果提示其可能用于多种癌症。然而,多项局限阻碍了TIL-ACT的临床开发和应用。综述范围:本文介绍TIL-ACT的原理,并讨论限制其治疗效力和广泛应用的主要因素,涵盖治疗耐药(先天性和获得性)、治疗相关毒性,以及肿瘤微环境(TME)代谢屏障这一新兴研究主题。专家观点:目前有多个研究方向致力于提高TIL-ACT临床疗效并优化治疗。其中许多策略潜力巨大,尤其是提高TIL疗效(例如体外增加并利用肿瘤反应性TIL亚群)以及改进生产工艺的策略。新方法有助于克服当前限制,并可能使TIL-ACT在多种肿瘤类型中成为主流癌症疗法。
INTRODUCTION: Adoptive cell therapy (ACT) with tumor-infiltrating lymphocytes (TILs) is a highly personalized type of cancer immunotherapy. TIL-based ACT exploits naturally occurring TILs, derived from the patients' tumor. This treatment has shown consistent clinical responses in melanoma, and recent results point toward a potential use in multiple cancer diagnoses.
However, several limitations have restricted the clinical development and adaptation of TIL-based ACT. AREAS COVERED: In this review, we present the principles of TIL-based ACT and discuss the most significant limitations for therapeutic efficacy and its widespread application. The topics of therapeutic resistance (both innate and acquired), treatment-related toxicity, and the novel research topic of metabolic barriers in the tumor microenvironment (TME) are covered.
EXPERT OPINION: There are many ongoing areas of research focusing on improving clinical efficacy and optimizing TIL-based ACT. Many strategies have shown a great potential, particularly strategies advancing TIL efficacy (such as increasing and harnessing ex vivo the sub-population of tumor-reactive TILs) and manufacturing processes. Novel approaches can help overcome current limitations and potentially result in TIL-based ACT entering the mainstream of cancer therapy across tumor types.
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