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Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma
release_nb4c2uszerh5xntr26diyufzw4
by
Daniel H. Shu,
Won Jin Ho,
Luciane Tsukamoto Kagohara,
Alexander Girgis,
Sarah M. Shin,
Ludmila Danilova,
Jae W. Lee,
Dimitrios Sidiropoulos,
Sarah Mitchell,
Kabeer Munjal,
Kathryn Howe,
Kayla J. Bendinelli
(+27 others)
Published
in Nature Immunology
by Springer Science and Business Media LLC.
2024 Volume 25, Issue 11, p2110-2123
Abstract
Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade, but understanding of the prognostic and predictive value of TLS and the circumstances of their resolution is incomplete. Here we show that in hepatocellular carcinoma treated with neoadjuvant immunotherapy, high intratumoral TLS density at the time of surgery is associated with pathologic response and improved relapse-free survival. In areas of tumor regression, we identify a noncanonical involuted morphology of TLS marked by dispersion of the B cell follicle, persistence of a T cell zone enriched for T cell-mature dendritic cell interactions and increased expression of T cell memory markers. Collectively, these data suggest that TLS can serve as both a prognostic and predictive marker of response to immunotherapy in hepatocellular carcinoma and that late-stage TLS may support T cell memory formation after elimination of a viable tumor.
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