Evaluating tumor-infiltrating lymphocytes in hepatocellular carcinoma using hematoxylin and eosin-stained tumor sections

e15613 Background: Within the tumor microenvironment (TME), infiltrating lymphocytes and myeloid cells including tumor-associated macrophages (TAMs) and tumor-associated neutrophils (TANs) are key players involved in liver cancer progression. The purpose of the study was to explorer whether distinct infiltrated immune cell features differentially affect clinical outcome in hepatocellular carcinoma (HCC). Methods: We obtained respectable stage II HCC specimens, along with adjacent para-tumor tissues from 221 patients who underwent surgical resection at Eastern Hepatobiliary Surgery Hospital, (in Shanghai, China) from 2015 through April 2018. CD8+, CD163+ and CD66B+ tumor-infiltrating lymphocytes (TILs) in the cancer area (CA) and stroma area (SA), as well paratumor stroma area, were analyzed by multiple immunohistochemistry. Results: Hierarchical clustering analysis of immune cell densities revealed that all HCC samples can be classified into three distinct groups. The three immune oncology types (IO-types) were characterized by a strong CD8 T cell density in CA and SA region (IO-1), an intermediate state of CD8 and CD163+ (IO-2), and a strong CD163+ macrophage density in IO-3. Remarkably increasing risks of mortality and recurrence, as well as elevated AST, ALP, GGT and AFP levels, were identified in IO-3 group, when compared with IO-1 group. We then identified that percentages of CA-CD8+ TILs in the tumor sample and SA-CD163+ macrophages in the para-tumor region showed opposite distribution pattern among the three IO types, suggesting a predictive role for CD8/TAM ratio in HCC cohort. Therefore, we next classified all HCC samples into two subgroups, according to the levels of tumor-CA-CD8/paratumor-SA-CD163 ratio. Expectedly, higher rate of CD8/CD163 represented significantly improved overall survival (OS) and progression free survival (PFS), verses lower rate of CD8/CD163. Further association studies suggested that the two subgroups correlated with HBV DNA, tumor size, and microvascular invasion (MVI). Of note, a prognostic signature combining portal vein tumor thrombus (PVTT) and CD8/CD163 ratio discriminated HCC patients into four subtypes with increasing risk of mortality and recurrence. Conclusions: The current results indicated that the CD8/CD163 is a novel, independent prognostic factor for a lower rate of disease recurrence and favorable OS in patients with resectable HCC.

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Tumor-infiltrating Lymphocytes and Prognosis of Hepatocellular Carcinoma

Japanese Journal of Clinical Oncology ◽

10.1093/oxfordjournals.jjco.a039559 ◽

1992 ◽

Keyword(s):

Hepatocellular Carcinoma ◽

Tumor Infiltrating Lymphocytes ◽

Infiltrating Lymphocytes

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TILs in rabbit mammary carcinomas

10.32545/encyclopedia202008.0012.v7 ◽

2020 ◽

Author(s):

Sandra Schöniger

Keyword(s):

Predictive Biomarkers ◽

Tumor Infiltrating Lymphocytes ◽

Tumor Grade ◽

Biological Behavior ◽

International Guidelines ◽

Mammary Carcinomas ◽

Tissue Sections ◽

Hematoxylin And Eosin ◽

Infiltrating Lymphocytes ◽

The Impact

Tumor infiltrating lymphocytes (TILs) are key components of the tumor microenvironment that mediate the anti-tumor immune response. In breast cancer of humans, TILs represent prognostic and predictive biomarkers. For their standardized evaluation in routinely (hematoxylin and eosin) stained tissue sections, international guidelines exist. Recently, TILs have also been analyzed in pet rabbit mammary carcinomas according to these international guidelines. Results of the study on rabbit mammary carcinomas showed a statistically significant association between higher TIL numbers in stromal TIL hotspot areas and microscopic parameters indicative of a better tumor differentiation, i.e. decreased mitotic count, lower histological tumor grade and higher percentage of calponin positive tumor cells. These findings suggest that in rabbit mammary carcinomas TIL hotspot areas may exert an influence on the biological behavior of these tumors. The present study contributes to comparative pathology. In addition, it provides the basis for further investigations into the impact of TILs on clinical parameters of pet rabbit mammary carcinomas.

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Nuclear Respiratory Factor 1 Associated with Prognosis and Immune Infiltration in Hepatocellular Carcinoma

10.21203/rs.3.rs-52843/v1 ◽

2020 ◽

Author(s):

Dan Wang ◽

Linlin Huang ◽

Xiaojing Zhang ◽

Pingping Sun ◽

Yapeng Lu ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

T Cells ◽

Chronic Hepatitis ◽

Mrna Expression ◽

Tumor Infiltrating Lymphocytes ◽

Cox Regression Analysis ◽

Nuclear Respiratory Factor ◽

Immune Infiltration ◽

Nuclear Respiratory Factor 1 ◽

Infiltrating Lymphocytes

Abstract Background: Recent studies have shown that functional mitochondria are essential for cancer cells. Nuclear respiratory factor 1 (NRF1) is a transcription factor that activates mitochondrial biogenesis and the expression of the respiratory chain, but little is known about its prognostic value and tumor-infiltrating lymphocytes association. Here, we evaluated the association among expression of NRF1, clinicopathological characteristics, survival and immune infiltration in hepatocellular carcinoma (HCC).Methods: We used the Tumor Immune Estimation Resource (TIMER) to analyze the difference of NRF1 mRNA expression in human cancers. Clinical-pathological information and follow-up data were collected from HCC (n = 171) and chronic hepatitis (n = 113) patients. NRF1 expression were scored based on the percentage and intensity of immunohistochemical staining in pathological slides. Correlations between clinical features and the expression of NRF1 were evaluated by Chi-square test, Kaplan-Meier curves, logrank tests and multivariate Cox regression analysis. The correlations between NRF1 expression and gene marker sets of tumor infiltrating lymphocytes (TILs) were analyzed by TIMER and Gene Expression Profiling Interactive Analysis (GEPIA) databases. Results: NRF1 mRNA expression was significantly higher in HCC than in normal tissue. Compared with chronic hepatitis, more frequency of NRF1 high expression are found in HCC (31.58 % vs 13.27 %, P < 0.001, P < 0.001). In addition, the NRF1 expression was significantly associated with hepatic cirrhosis (P = 0.021) and vascular invasion (P = 0.025). NRF1 expression was also a significant independent predictor of survival in HCC (P = 0.003; HRadj = 0.20; 95% CI = 0.09 – 0.44). NRF1 showed positively correlated with TILs, including B cell (r = 0.384, P = 1.68e-13), CD8+ T cells (r = 0.246, P = 3.99e-06), CD4+ T cells (r = 0.535, P = 6.90e-27), macrophage (r = 0.506, P = 1.52e-23), neutrophils (r = 0.465, P = 6.08e-20) and dendritic cell (r = 0.404, P = 8.61e-15). The marker genes of TILs correlated significantly with NRF1 expression.Conclusions: NRF1 expression was a useful independent prognostic factor and correlated with tumor immune infiltration in HCC.

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