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Late-stage tertiary lymphoid structures in hepatocellular carcinoma treated with neoadjuvant immune checkpoint blockade [bulk RNA-seq]

ABSTRACT: Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade (ICB), but understanding of their clinical significance and the circumstances of their resolution remains incomplete. Here, we found that in hepatocellular carcinoma (HCC) 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 further identified a non-canonical 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 may serve be both a prognostic and predictive marker of response to immunotherapy in HCC and suggest a functional role for late-stage TLS T cell memory formation after elimination of viable tumor.

ORGANISM(S): Homo sapiens

PROVIDER: GSE272346 | GEO | 2024/09/13

REPOSITORIES: GEO

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Late-stage tertiary lymphoid structures in hepatocellular carcinoma treated with neoadjuvant immune checkpoint blockade [scRNA-seq]

Project description:Tertiary lymphoid structures (TLS) are associated with improved response in solid tumors treated with immune checkpoint blockade (ICB), but understanding of their clinical significance and the circumstances of their resolution remains incomplete. Here, we found that in hepatocellular carcinoma (HCC) 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 further identified a non-canonical 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 may serve be both a prognostic and predictive marker of response to immunotherapy in HCC and suggest a functional role for late-stage TLS T cell memory formation after elimination of viable tumor.

2024-09-13 | GSE272347 | GEO

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Project description:Most high grade serous ovarian cancers (HGSOC) originate in the fallopian tube but spread to the ovary and peritoneal cavity, highlighting the need to understand antitumor immunity across HGSOC sites. Using spatial analyses, we discover that tertiary lymphoid structures (TLS) within ovarian tumors are less developed compared with TLS in fallopian tube or omental tumors. We reveal transcriptional differences across a spectrum of lymphoid structures, demonstrating that immune cell activity increases when residing in more developed TLS and produce a prognostic, spatially derived TLS signature from HGSOC tumors. We interrogate TLS-adjacent stroma and assess how normal mesenchymal stem cells MSCs (nMSCs) may support B cell function and TLS, contrary to cancer-educated MSCs (CA-MSCs) which negate the prognostic benefit of our TLS signature, suggesting that pro-tumorigenic stroma could limit TLS formation.

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