Cancer Immunotherapy and Biomarkers
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The spleen is identified as an important site for generating a tumor-specific T cell response after immune checkpoint blockade, and the critical role of antigen density within the spleen for the differentiation and expansion of T cell clonotypes in response to ICB is demonstrated.
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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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@article{Morgan2024Expansion,
title = {Expansion of tumor-reactive CD8 + T cell clonotypes occurs in the spleen in response to immune checkpoint blockade},
author = {Duncan M. Morgan and Brendan Horton and Vidit Bhandarkar and Richard Van and Teresa Dinter and Maria Zagorulya and J. Christopher Love and Stefani Spranger},
journal = {Science Immunology},
year = {2024},
doi = {10.1126/sciimmunol.adi3487},
url = {https://doi.org/10.1126/sciimmunol.adi3487}
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