TY - JOUR
T1 - Immunotherapy response induces divergent tertiary lymphoid structure morphologies in hepatocellular carcinoma
AU - Shu, Daniel H.
AU - Ho, Won Jin
AU - Kagohara, Luciane T.
AU - Girgis, Alexander
AU - Shin, Sarah M.
AU - Danilova, Ludmila
AU - Lee, Jae W.
AU - Sidiropoulos, Dimitrios N.
AU - Mitchell, Sarah
AU - Munjal, Kabeer
AU - Howe, Kathryn
AU - Bendinelli, Kayla J.
AU - Kartalia, Emma
AU - Qi, Hanfei
AU - Mo, Guanglan
AU - Montagne, Janelle
AU - Leatherman, James M.
AU - Lopez-Vidal, Tamara Y.
AU - Zhu, Qingfeng
AU - Huff, Amanda L.
AU - Yuan, Xuan
AU - Hernandez, Alexei
AU - Coyne, Erin M.
AU - Zaidi, Neeha
AU - Zabransky, Daniel J.
AU - Engle, Logan L.
AU - Ogurtsova, Aleksandra
AU - Baretti, Marina
AU - Laheru, Daniel
AU - Durham, Jennifer N.
AU - Wang, Hao
AU - Sunshine, Joel C.
AU - Johnston, Robert J.
AU - Deutsch, Julie Stein
AU - Taube, Janis M.
AU - Anders, Robert A.
AU - Jaffee, Elizabeth M.
AU - Fertig, Elana J.
AU - Yarchoan, Mark
N1 - Publisher Copyright:
© The Author(s), under exclusive licence to Springer Nature America, Inc. 2024.
PY - 2024/11
Y1 - 2024/11
N2 - 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.
AB - 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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U2 - 10.1038/s41590-024-01992-w
DO - 10.1038/s41590-024-01992-w
M3 - Article
C2 - 39455893
AN - SCOPUS:85207367988
SN - 1529-2908
VL - 25
SP - 2110
EP - 2123
JO - Nature Immunology
JF - Nature Immunology
IS - 11
ER -