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. Author manuscript; available in PMC: 2025 Aug 27.
Published in final edited form as: Semin Liver Dis. 2025 Mar 5;45(1):33–51. doi: 10.1055/a-2551-0724

Figure 2. Spatial differences in fibroblasts location between HCC and iCCA.

Figure 2.

Activated HSCs accumulate in the premalignant environment (PME) in most HCC cases, with limited infiltration into the tumor microenvironment (TME). CyHSCs, myHSCs, pHSCs, and SenHSCs subtypes, contribute to the pro-fibrotic PME milieu, by directly and indirectly supporting tumor initiation and progression. In iCCA HSC-derived CAFs are abundant and accumulate within the tumor mass in the TME, where myCAFs are the most abundant subtype followed by iCAFs. Other CAF subtypes such as apCAf, vCAFs, eCAFs, lCAFs, and eventually SenCAFs, have been also described in the TME of iCCA.

apCAF, Antigen presenting CAF; CAF, Cancer associated fibroblast; cyHSC, cytokine HSC; eCAF, EMT-like CAF; iCAF, Inflammatory CAF; lCAF, lipo-fibroblasts; mesCAF, mesotelial CAF; myCAF, myofibroblastic CAFs; myHSC, myofibroblastic HSC; pHSC, proliferative HSC; PME, Premalignant environment; SenCAF, senescent CAF; TME, Tumor microenvironment; vCAF, vascular CAF.