小柯机器人

加拿大卡尔加里大学Nizar J. Bahlis和德国海德堡大学Marc-Steffen Raab研究组合作揭示，现有的T细胞格局决定了多发性骨髓瘤患者对双特异性T细胞接合物(TCEs)的反应。相关论文于2023年3月9日发表在《癌细胞》杂志上。

他们确定了骨髓T细胞在接受BCMAxCD3 TCE治疗的多发性骨髓瘤患者中的保守行为。他们发现，免疫库对TCE治疗的反应是细胞状态依赖的克隆扩增，并发现证据支持通过主要组织相容性复合体I类(MHC I类)、衰竭和临床反应来耦合肿瘤识别。他们发现衰竭样CD8+ T细胞克隆的丰度与临床反应失败相关，他们将靶表位和MHC类I的缺失描述为肿瘤对TCEs的内在适应。这些发现促进了人们对人体TCE治疗的体内机制的理解，并为预测免疫监测和调节免疫库提供了理论基础，以指导未来恶性血液病的免疫治疗。

据悉，双特异性TCEs在各种癌症的治疗中显示出了希望，但对TCEs的原发性和获得性耐药的免疫机制和分子决定因素仍然知之甚少。

附：英文原文

Title: The pre-existing T cell landscape determines the response to bispecific T cell engagers in multiple myeloma patients

Author: Mirco J. Friedrich, Paola Neri, Niklas Kehl, Julius Michel, Simon Steiger, Michael Kilian, Noémie Leblay, Ranjan Maity, Roman Sankowski, Holly Lee, Elie Barakat, Sungwoo Ahn, Niels Weinhold, Karsten Rippe, Lukas Bunse, Michael Platten, Hartmut Goldschmidt, Carsten Müller-Tidow, Marc-Steffen Raab, Nizar J. Bahlis

Issue&Volume: 2023-03-09

Abstract: Bispecific T cell engagers (TCEs) have shown promise in the treatment of various cancers, but the immunological mechanism and molecular determinants of primary and acquired resistance to TCEs remain poorly understood. Here, we identify conserved behaviors of bone marrow-residing T cells in multiple myeloma patients undergoing BCMAxCD3 TCE therapy. We show that the immune repertoire reacts to TCE therapy with cell state-dependent clonal expansion and find evidence supporting the coupling of tumor recognition via major histocompatibility complex class I (MHC class I), exhaustion, and clinical response. We find the abundance of exhausted-like CD8+ T cell clones to be associated with clinical response failure, and we describe loss of target epitope and MHC class I as tumor-intrinsic adaptations to TCEs. These findings advance our understanding of the in vivo mechanism of TCE treatment in humans and provide the rationale for predictive immune-monitoring and conditioning of the immune repertoire to guide future immunotherapy in hematological malignancies.

DOI: 10.1016/j.ccell.2023.02.008

Source: https://www.cell.com/cancer-cell/fulltext/S1535-6108(23)00036-3

Cancer Cell：《癌细胞》，创刊于2002年。隶属于细胞出版社，最新IF：38.585
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