T- and B-Cells in the Inner Invasive Margin of Hepatocellular Carcinoma after Resection Associate with Favorable Prognosis

Trailin, Andriy; Červenková, Lenka; Ambrożkiewicz, Filip; Ali, Esraa; Kasi, Phanindra Babu; Pálek, Richard; Hošek, Petr; Třeška, Vladislav; Daum, Ondřej; Tonar, Zbyněk; Liška, Václav; Hemminki, Kari

doi:10.3390/cancers14030604

Cited by 5 publications

(9 citation statements)

References 38 publications

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“…For each patient FFPE tissue blocks containing center of the tumor (TC) and invasive margin (IM) and, when available, separate block with non-tumor liver, 2-to 3-cm distant from the tumor site, were retrieved from the pathology archive; the detailed procedure are described elsewhere [25]. One or two tis-sue sections of 4-μm thickness were cut and mounted onto BOND Plus microscope slides (K8020, Leica Bio-systems Newcastle Ltd., United Kingdom).…”

Section: Histology and Immunohistochemistrymentioning

confidence: 99%

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CTNNB1 mutations, TERT polymorphism and CD8+ cell densities in resected hepatocellular carcinoma are associated with longer time to recurrence

et al. 2022

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Background Hepatocellular carcinoma (HCC) is a fatal disease characterized by early genetic alterations in telomerase reverse transcriptase promoter (TERTp) and β-catenin (CTNNB1) genes and immune cell activation in the tumor microenvironment. As a novel approach, we wanted to assess patient survival influenced by combined presence of mutations and densities of CD8+ cytotoxic T cells. Methods Tissue samples were obtained from 67 HCC patients who had undergone resection. We analysed CD8+ T cells density, TERTp mutations, rs2853669 polymorphism, and CTNNB1 mutations. These variables were evaluated for time to recurrence (TTR) and disease free survival (DFS). Results TERTp mutations were found in 75.8% and CTNNB1 mutations in 35.6% of the patients. TERTp mutations were not associated with survival but polymorphism rs2853669 in TERTp was associated with improved TTR and DFS. CTNNB1 mutations were associated with improving TTR. High density of CD8+ T-lymphocytes in tumor center and invasive margin correlated with longer TTR and DFS. Combined genetic and immune factors further improved survival showing higher predictive values. E.g., combining CTNNB1 mutations and high density of CD8+ T-lymphocytes in tumor center yielded HRs of 0.12 (0.03–0.52), p = 0.005 for TTR and 0.25 (0.09–0.74), p = 0.01 for DFS. Conclusion The results outline a novel integrative approach for prognostication through combining independent predictive factors from genetic and immune cell profiles. However, larger studies are needed to explore multiple cell types in the tumor microenvironment.

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Section: Histology and Immunohistochemistrymentioning

confidence: 99%

“…We did not detect any correlations between mutations and the polymorphism. Clinical data were discussed in more detail in our previous work (25); only TNM stage (HR = 1.5. p = 0.032) and age (HR = 0.96, p = 0.007) had impact on patients TTR.…”

Section: Tert Promoter and Ctnnb1 Mutations And Polymorphism Rs2853669mentioning

confidence: 99%

CTNNB1 mutations, TERT polymorphism and CD8+ cell densities in resected hepatocellular carcinoma are associated with longer time to recurrence

et al. 2022

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“…IHC was conducted in the BLCA specimen using the monoclonal antibody against CD20 (dilution: 1:100, ABclonal, China). The B cells in the slides were distinguished from other cells by staining of CD20, as reported by previous studies [ 22 , 23 ]. The detailed processes of IHC in the BLCA tissue slides were well described in our earlier study [ 24 ].…”

Section: Methodsmentioning

confidence: 95%

Construction and experimental validation of a B cell-related gene signature to predict the prognosis and immunotherapeutic sensitivity in bladder cancer

Zhou

Muhuitijiang

et al. 2023

Aging

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Background: B cells are essential components of tumor microenvironment and exert important functions in anti-tumor immune response. However, the prognosis value of B cell-related genes in bladder cancer (BLCA) remains obscure. Materials and Methods: The infiltrating levels of B cells were measured via the CD20 staining in the local samples and the computational biology analyses in the TCGA-BLCA cohort. The single-cell RNA sequencing analysis, gene-pair strategy, LASSO regression, random forest, and Cox regression were used for B cell-related signature construction. TCGA-BLCA cohort was chosen as the training cohort, and three independent cohorts from GEO and the local cohort were used for external validation. 326 B cells were adopted to explore the association between the model and B cells' biological processes. TIDE algorithm and two BLCA cohorts receiving anti-PD1/PDL1 treatment were utilized to detect its predictive ability to the immunotherapeutic response. Results: High infiltration levels of B cells heralded favorable prognosis, both in the TCGA-BLCA cohort and the local cohort (all P < 0.05). A 5-gene-pair model was established and served as a significant prognosis predictor across multiple cohorts (pooled hazard ratio = 2.79, 95% confidence interval = 2.22-3.49). The model could evaluate the prognosis effectively in 21 of 33 cancer types (P < 0.05). The signature was negatively associated with B cells' activation, proliferation, and infiltrating levels, and could serve as a potential predictor of immunotherapeutic outcomes. Conclusions: A B cell-related gene signature was constructed to predict the prognosis and immunotherapeutic sensitivity in BLCA, helping to guide the personalized treatment.

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“…When defining ROIs, we followed the recommendations of the International Immunooncology Biomarkers Working Group [31]. Inner margin (IM) and outer margin (OM) were extended automatically as 500 μm-wide regions on each side of the border [2]. The tumor center (TC) represents the remaining tumor area.…”

Section: Image Analysismentioning

confidence: 99%

“…Liver cancer, which in 75-85% of cases is represented by hepatocellular carcinoma (HCC), ranks as the third leading cause of cancer death worldwide [1]. The type, density, and location of adaptive immune cells within the tumor microenvironment (TME) have been reported to improve the estimation of HCC prognosis with the contribution of the commonly used tools of tumornode-metastasis (TNM) staging, microvascular invasion, tumor multiplicity, and serum α-fetoprotein level [2]. Innate immune cells in TME could also improve the prediction of clinical outcomes in different cancers [3].…”

Section: Introductionmentioning

confidence: 99%

Prognostic role of macrophages and mast cells in the microenvironment of hepatocellular carcinoma after resection

Ali,

Červenková,

Pálek

et al. 2024

BMC Cancer

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Background The prognostic significance of mast cells and different phenotypes of macrophages in the microenvironment of hepatocellular carcinoma (HCC) following resection is unclear. We aimed in this study to assess the local distribution of infiltrating macrophages and mast cells of specific phenotypes in tissues of HCC and to evaluate their prognostic values for survival of post-surgical patients. Methods The clinicopathological and follow-up data of 70 patients with HCC, who underwent curative resection of tumor from 1997 to 2019, were collected. The infiltration of CD68+ and CD163+ macrophages and CD117+ mast cells was assessed immunohistochemically in representative resected specimens of HCC and adjacent tissues. The area fraction (AF) of positively stained cells was estimated automatically using QuPath image analysis software in several regions, such as tumor center (TC), inner margin (IM), outer margin (OM), and peritumor (PT) area. The prognostic significance of immune cells, individually and in associations, for time to recurrence (TTR), disease-free survival (DFS), and overall survival (OS) was evaluated using Kaplan-Meier and Cox regression analyses. Results High AF of CD68+ macrophages in TC and IM and high AF of mast cells in IM and PT area were associated with a longer DFS. High AF of CD163+ macrophages in PT area correlated with a shorter DFS. Patients from CD163TChigh & CD68TClow group had a shorter DFS compared to all the rest of the groups, and cases with CD163IMlow & CD68IMhigh demonstrated significantly longer DFS compared to low AF of both markers. Patients from CD68IMhigh & CD163PTlow group, CD117IMhigh & CD163PTlow group, and CD117PThigh & CD163PTlow group had a significantly longer DFS compared to all other combinations of respective cells. Conclusions The individual prognostic impact of CD68+ and CD163+ macrophages and mast cells in the microenvironment of HCC after resection depends on their abundance and location, whereas the cumulative impact is built upon combination of different cell phenotypes within and between regions.

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T- and B-Cells in the Inner Invasive Margin of Hepatocellular Carcinoma after Resection Associate with Favorable Prognosis

Cited by 5 publications

References 38 publications

CTNNB1 mutations, TERT polymorphism and CD8+ cell densities in resected hepatocellular carcinoma are associated with longer time to recurrence

CTNNB1 mutations, TERT polymorphism and CD8+ cell densities in resected hepatocellular carcinoma are associated with longer time to recurrence

Construction and experimental validation of a B cell-related gene signature to predict the prognosis and immunotherapeutic sensitivity in bladder cancer

Prognostic role of macrophages and mast cells in the microenvironment of hepatocellular carcinoma after resection

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