Duncan M. Morgan, Brendan L. Horton, Vidit Bhandarkar, Richard Van, Teresa Dinter, Maria Zagorulya, J. Christopher Love, Stefani Spranger
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引用次数: 0
Abstract
Immune checkpoint blockade (ICB) enhances T cell responses against cancer, leading to long-term survival in a fraction of patients. CD8+ T cell differentiation in response to chronic antigen stimulation is highly complex, and it remains unclear precisely which T cell differentiation states at which anatomic sites are critical for the response to ICB. We identified an intermediate-exhausted population in the white pulp of the spleen that underwent substantial expansion in response to ICB and gave rise to tumor-infiltrating clonotypes. Increased systemic antigen redirected differentiation of this population toward a more circulatory exhausted KLR state, whereas a lack of cross-presented tumor antigen reduced its differentiation in the spleen. An analogous population of exhausted KLR CD8+ T cells in human blood samples exhibited diminished tumor-trafficking ability. Collectively, our data demonstrate the critical role of antigen density within the spleen for the differentiation and expansion of T cell clonotypes in response to ICB.
免疫检查点阻断(ICB)可增强T细胞对癌症的反应,从而使一部分患者长期存活。应对慢性抗原刺激的 CD8+ T 细胞分化非常复杂,目前仍不清楚哪些解剖部位的 T 细胞分化状态对 ICB 的反应至关重要。我们在脾脏白髓中发现了一个中间衰竭群体,它在对 ICB 作出反应时发生了大量扩增,并产生了肿瘤浸润克隆型。全身抗原的增加使这一群体向循环衰竭的 KLR 状态重新分化,而交叉呈现的肿瘤抗原的缺乏则减少了其在脾脏中的分化。人体血液样本中类似的枯竭 KLR CD8+ T 细胞群表现出较低的肿瘤牵引能力。总之,我们的数据证明了脾脏内的抗原密度对 T 细胞克隆型对 ICB 的分化和扩增起着至关重要的作用。
期刊介绍:
Science Immunology is a peer-reviewed journal that publishes original research articles in the field of immunology. The journal encourages the submission of research findings from all areas of immunology, including studies on innate and adaptive immunity, immune cell development and differentiation, immunogenomics, systems immunology, structural immunology, antigen presentation, immunometabolism, and mucosal immunology. Additionally, the journal covers research on immune contributions to health and disease, such as host defense, inflammation, cancer immunology, autoimmunity, allergy, transplantation, and immunodeficiency. Science Immunology maintains the same high-quality standard as other journals in the Science family and aims to facilitate understanding of the immune system by showcasing innovative advances in immunology research from all organisms and model systems, including humans.