Abstract: Membrane proteins, which play a critical role in various life processes, particularly in regulating cell-cell contact and signal transduction, are closely linked to cell differentiation and maturation. Therefore, it is of great theoretical and practical significance to develop a variety of methods to thoroughly explore the interactions between membrane proteins. In addition to traditional techniques such as immunoprecipitation, newly developed proximity labeling (PL) techniques have gradually become important means to study membrane protein interaction. PL methods are based on engineered enzymes fused with bait protein to catalyze small molecules, label neighboring target proteins, and detect the interactions by flow cytometry, mass spectrometry, confocal microscopic imaging, etc. This paper focuses on the recent developments in PL techniques for studying membrane protein interactions, with a prospect of the potential future directions for research in this area.

The efficacy of adaptive immune responses in cancer treatment relies heavily on the state of the T cells. Upon antigen exposure, T cells undergo metabolic reprogramming, leading to the development of functional effectors or memory populations. However, within the tumor microenvironment (TME), metabolic stress impairs CD8 + T cell anti-tumor immunity, resulting in exhausted differentiation. Recent studies suggested that targeting T cell metabolism could offer promising therapeutic opportunities to enhance T cell immunotherapy. In this review, we provide a comprehensive summary of the intrinsic and extrinsic factors necessary for metabolic reprogramming during the development of effector and memory T cells in response to acute and chronic inflammatory conditions. Furthermore, we delved into the different metabolic switches that occur during T cell exhaustion, exploring how prolonged metabolic stress within the TME triggers alterations in cellular metabolism and the epigenetic landscape that contribute to T cell exhaustion, ultimately leading to a persistently exhausted state. Understanding the intricate relationship between T cell metabolism and cancer immunotherapy can lead to the development of novel approaches to improve the efficacy of T cell-based treatments against cancer.

[摘 要] 过继性T细胞疗法在实体瘤治疗中展现了良好的前景，成为目前肿瘤治疗领域的一大研究热点。其中，TCR-T疗法主要通过T细胞受体（TCR）与抗原肽-主要组织相容性复合体（pMHC）的特异性识别，进而激活过继性T细胞的抗肿瘤免疫反应。因此，全面解析TCR所靶向的抗原信息有助于提高TCR-T疗法在临床应用中的有效性及安全性。然而，高效、高通量的TCR抗原筛选技术的缺乏限制了TCR-T疗法的发展。近年来，随着高通量测序技术、质谱流式细胞技术和计算生物学的快速发展，研究人员开发了多种TCR抗原筛选技术用于解析TCR及其特异性识别的抗原信息。本文从抗原定向筛选、TCR定向筛选以及双向筛选三方面对TCR抗原筛选技术进行归纳总结，系统介绍其优缺点，展望TCR抗原筛选技术领域的发展前景，为未来抗原筛选技术的开发提供了新思路。