脾脏
免疫学
生物
CD8型
抗原
免疫系统
人口
细胞毒性T细胞
封锁
白浆
免疫检查点
T细胞
癌症研究
免疫疗法
医学
受体
生物化学
环境卫生
体外
作者
Duncan M. Morgan,Brendan Horton,Vidit Bhandarkar,Richard Van,Teresa Dinter,Maria Zagorulya,J. Christopher Love,Stefani Spranger
出处
期刊:Science immunology
[American Association for the Advancement of Science (AAAS)]
日期:2024-09-13
卷期号:9 (99)
标识
DOI:10.1126/sciimmunol.adi3487
摘要
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.
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