journal contribution
posted on 2024-12-16, 08:20 authored by Yutaka Kurebayashi, Katsutoshi Sugimoto, Hanako Tsujikawa, Kosuke Matsuda, Rui Nomura, Akihisa Ueno, Yohei Masugi, Ken Yamazaki, Kathryn Effendi, Hirohito Takeuchi, Takao Itoi, Yasushi Hasegawa, Yuta Abe, Minoru Kitago, Hidenori Ojima, Michiie Sakamoto Table S9. Primers used in this study
Funding
Japan Society for the Promotion of Science (JSPS)
Japan Agency for Medical Research and Development (AMED)
Keio University Academic Development Funds
Keio University Medical Science Fund
Foundation for Promotion of Cancer Research
History
ARTICLE ABSTRACT
Immunotherapies have led to a paradigm shift in the treatment of hepatocellular carcinoma (HCC). Studies have revealed the single-cell catalogs of tumor-infiltrating immune cells and the trajectories of their differentiation. Nevertheless, the spatial distribution of these immune cells with distinct phenotypes in the tumor microenvironment and their clinicopathologic significance in resectable and unresectable HCCs are still largely unclear.
We analyzed the spatial dynamics of intratumoral CD4 and CD8 T cells and their association with B and plasma cells using 283 surgically resected HCC samples, 58 unresectable HCC samples before combined immunotherapy [atezolizumab plus bevacizumab (Atezo + Bev)], and autopsy specimens from 50 cases of advanced-stage HCC through multiplex IHC combined with transcriptomic and driver gene mutation analyses. Classification based on the spatial dynamics of T- and B-cell responses (refined immunosubtype) was developed, and its clinicopathologic significance was analyzed.
We found that stem-like CD4 and CD8 T cells were mainly observed in T-cell aggregates and T-cell zone of tertiary lymphoid structure (TLS). The differentiation of T follicular helper cells was associated with the development of TLS, whereas the differentiation of CXCL13-expressing CD4 TCXCL13 cells with a phenotype resembling T peripheral helper cells was associated with the development of the lymphoplasmacytic microenvironment. The refined immunosubtype could predict clinical outcomes of resectable HCC after surgery and unresectable HCC after Atezo + Bev therapy. The immune microenvironment of metastatic lesions tended to reflect those of primary lesions.
We revealed the spatial dynamics of T- and B-cell responses in HCC, which is closely associated with the clinical outcome after surgical resection or Atezo + Bev therapy.
