Comparison of immune profiles between hepatocellular carcinoma subtypes

Pan, Xiao; Lin, Ping; Feng, Fangyoumin; Li, Jia; Li, Yuanyuan; Dai, Wentao; Hu, Bo; Yang, Xin‐Rong; Fan, Jia; Li, Hong; Li, Yixue

doi:10.1007/s41048-019-00102-w

Cited by 2 publications

(3 citation statements)

References 54 publications

(59 reference statements)

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“…13 The TME varies depending on the specific tumour subtype, and it is considered to affect the biological behaviour of HCCs. 14,15 Along with this concept, individual tumours have variable tissue tropisms for metastasis, classically known as the seed-and-soil theory. 16,17 Each organ varies not only in its physical location but also in its stromal niche, that is, the vascular and nutrient supply, extracellular matrix elements, and pre-occupying immune cells; therefore, each tumour type has its own metastatic pattern and preference for specific organs.…”

Section: Introductionmentioning

confidence: 99%

“…Intimate interactions among these cells have an influence on the biological behaviour of the tumour 13 . The TME varies depending on the specific tumour subtype, and it is considered to affect the biological behaviour of HCCs 14,15 . Along with this concept, individual tumours have variable tissue tropisms for metastasis, classically known as the seed‐and‐soil theory 16,17 .…”

Section: Introductionmentioning

confidence: 99%

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Lung and lymph node metastases from hepatocellular carcinoma: Comparison of pathological aspects

Woo

Rhee

Yoo

et al. 2021

Liver International

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Background & Aims: Extrahepatic metastasis from hepatocellular carcinoma (HCC) is a catastrophic event, yet organ-specific pathological characteristics of metastatic HCC remain unclear. We aimed to characterize the pathological aspects of HCC metastases to various organs. Methods:We collected intrahepatic HCC (cohort 1, n = 322) and extrahepatic metastatic HCC (cohort 2, n = 130) samples. Clinicopathological evaluation and immunostaining for K19, CD34, αSMA, fibroblast-associated protein (FAP), CAIX, VEGF, PD-L1, CD3, CD8, Foxp3, CD163 and epithelial-mesenchymal transition (EMT)related markers were performed.Results: Independent factors for extrahepatic metastasis included BCLC stage B-C, microvascular invasion (MVI), vessels encapsulating tumour clusters (VETC)-HCC, K19 and FAP expression, and CD163+ macrophage infiltration (cohort 1, P < .05 for all). Lung metastases (n = 63) had the highest proportion of VETC-HCC and macrotrabecular-massive (MTM)-HCC. Lymph node metastases (n = 19) showed significantly high rates of EMT-high features, K19 expression, fibrous tumour stroma with αSMA and FAP expression, high immune cell infiltration, PD-L1 expression (combined positive score), CD3+, CD8+, Foxp3+ T cell and CD163+ macrophage infiltration (adjusted P < .05 for all). In both cohorts, EMT-high HCCs showed higher rates of K19 expression, fibrous tumour stroma, high immune cell infiltration, PD-L1 expression and CD3+ T cell infiltration, whereas EMT-low HCCs were more frequent among VETC-HCCs (P < .05 for all). Overall phenotypic features were not significantly different between paired primary-metastatic HCCs (n = 32).Conclusions: Metastatic HCCs to various organs showed different pathological features. VETC and MTM subtypes were related to lung metastasis, whereas K19 expression, EMT-high features with fibrous tumour stroma and high immune cell infiltration were related to lymph node metastasis.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Lung and lymph node metastases from hepatocellular carcinoma: Comparison of pathological aspects

Woo

Rhee

Yoo

et al. 2021

Liver International

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“…Immunotherapy in solid tumors: from the beginning in 2010 to now in advanced HCC in cirrhosis After the intratumoral immune cell microenvironment directed attention of scientists toward HCC [50][51][52] , the therapeutic use of the so-called checkpoint inhibitors, also defined as immunotherapy, in patients with HCC in cirrhosis has matured [53] .…”

Section: Hcc Systemic Intravenous Therapy With Monoclonal Antibodiesmentioning

confidence: 99%

C-kit expression in cancer cells or hematopoietic cells of the tumoral microenvironment: which is the basis for efficacy of TK inhibitors and immunotherapy in HCC?

Ramadori¹

2021

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Twenty years ago, hematologists introduced imatinib, a tyrosine kinase inhibitor (TKI), as a long-term oral systemic therapy for patients suffering from chronic myeloid leukemia (CML) and gastrointestinal stroma tumor (GIST) (400 mg/day) who have normal liver function. The mechanism of action of imatinib was considered to be the specific interruption of the activation of the BCR-ABL kinase in CML patients and the autoactivated c-kittyrosine kinase in GIST patients. After the first successful long-term treatment of a c-kit-positive HCC patient with imatinib, 10 further patients with unresectable HCC were treated in Göttingen. After 18 months of therapy (200 mg/day), four patients remained alive. The first approval of a TKI, sorafenib, occurred in 2008 and several other TKIs have been approved since for patients with advanced HCC and CHILD A cirrhosis. As immune cells of the tumoral microenvironment (c-kit positive or PD-1-and PD-L1 positive) can contribute to cancer cell survival, it could be assumed that those cells are the real target not only of TKIs but also of recently approved monoclonal antibodies. In fact, histological studies of the first treated GIST in Finland and the first HCC patient treated in Göttingen showed similar results, acellular necrotic material. As most patients with HCC are older than those recruited for the studies published thus far and systemic therapy duration is quite short, imatinib at a lower dose (200 mg/day) may be an additional alternative in long-term treatment of HCC/cholangiocellular carcinoma in patients unfit for resection or transplantation and who are unresponsive or intolerant of other treatments.

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Comparison of immune profiles between hepatocellular carcinoma subtypes

Cited by 2 publications

References 54 publications

Lung and lymph node metastases from hepatocellular carcinoma: Comparison of pathological aspects

Lung and lymph node metastases from hepatocellular carcinoma: Comparison of pathological aspects

C-kit expression in cancer cells or hematopoietic cells of the tumoral microenvironment: which is the basis for efficacy of TK inhibitors and immunotherapy in HCC?

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