The Prognostic Value of Tumor-infiltrating Lymphocytes in Hepatocellular Carcinoma: a Systematic Review and Meta-analysis

Yao, Wei; He, Jin; Yang, Yan; Wang, Jianming; Qian, Yawei; Yang, Tao; Ji, Lei

doi:10.1038/s41598-017-08128-1

Cited by 118 publications

(108 citation statements)

References 53 publications

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“…Tumorinfiltrating lymphocytes (TILs) may represent important antitumor effector cells associated with improved prognosis. (23) In the present study, the LMR decreased 1 month after LDLT in almost all of the patients, and the LMR increased again 1 year after LDLT. These findings indicate that immunosuppression after LDLT caused the decrease in LMR, and the reduction of immunosuppression 1 year after LDLT caused LMR to increase.…”

Section: Discussionsupporting

confidence: 64%

“…Generally, cytokines and chemokines produced by cancer cells reflect inflammation that occurs locally and systemically during cancer progression. Tumor‐infiltrating lymphocytes (TILs) may represent important antitumor effector cells associated with improved prognosis . In the present study, the LMR decreased 1 month after LDLT in almost all of the patients, and the LMR increased again 1 year after LDLT.…”

Section: Discussionmentioning

confidence: 99%

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Lymphocyte‐to‐Monocyte Ratio Is a Predictor of Survival After Liver Transplantation for Hepatocellular Carcinoma

et al. 2018

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Recent studies revealed that systemic inflammation was correlated with poorer prognosis in various cancers. We investigated the prognostic value of the lymphocyte-to-monocyte ratio (LMR) in patients who underwent living donor liver transplantation (LDLT) for hepatocellular carcinoma (HCC). We retrospectively analyzed the records of 216 patients who underwent LDLT for HCC. Patients were divided into high (n = 126) and low (n = 90) LMR groups. Their clinicopathological parameters and survival times were compared. To determine the mechanisms of the change in the LMR, we performed immunohistochemical analyses of CD3 and CD68 expression. A low LMR was significantly associated with a high Model for End-Stage Liver Disease score; a high Child-Pugh score; elevation of alpha-fetoprotein, des-gamma-carboxyprothrombin, and neutrophil-to-lymphocyte ratio; larger tumor size; more tumors; and poorer prognosis. A low LMR was associated with poor prognosis and represented an independent prognostic factor, particularly among patients beyond the Milan criteria. The ratio of CD3-positive to CD68-positive cells was significantly lower in the low-LMR group. In conclusion, our results show that the LMR was an independent predictor of survival of patients with HCC beyond the Milan criteria who underwent LDLT. The LMR reflected the immune status of the tumor microenvironment.

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Section: Discussionsupporting

confidence: 64%

Section: Discussionmentioning

confidence: 99%

Lymphocyte‐to‐Monocyte Ratio Is a Predictor of Survival After Liver Transplantation for Hepatocellular Carcinoma

et al. 2018

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“…Mao et al found that CD8 + TILs were associated with improved DFS, while FOXP3+ TILs were associated with reduced DFS in breast cancer [54]. Yao et al reported that high levels of CD8 + and CD3 + TILs had a better prognostic value on OS and DFS, whereas high levels of FoxP3 + TILs had a worse prognostic value on OS and DFS [55]. In contrast, our study found that CD4 + had no prognostic value and high level of FOXP3 + TILs was associated with better DFS.…”

Section: Discussionmentioning

confidence: 99%

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Zheng¹,

Song

Shao

et al. 2018

Cell Physiol Biochem

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Background/Aims: Several studies have verified the correlation between tumor-infiltrating lymphocytes (TILs) and survival of patients with esophagus cancer (EC). However, the prognostic role of TILs is still controversial. Therefore, we performed this meta-analysis. Methods: We searched PubMed, Embase and the Cochrane Library (last update by August 30, 2017) to identify studies assessing the effect of TILs on survival of patients with EC. Pooled hazard ratios (HRs) for overall survival (OS), disease-free survival (DFS) and cancer specific survival (CSS) were estimated using fixed-effects models or random-effects models, which depends on the heterogeneity. Results: Data from 22 observational studies including 2909 patients were summarized. Pooled analysis indicated that generalized TILs were favorable prognostic markers for OS in patients with EC (pooled HR = 0.48; 95% CI = 0.38-0.61; P < 0.001). For TIL subsets, CD8⁺ TILs were associated with improved OS (pooled HR = 0.68; 95% CI = 0.58–0.84; P < 0.001) and DFS (pooled HR = 0.90; 95% CI = 0.85-0.95; P < 0.001); FoxP3⁺ TILs were associated with patients’ DFS (pooled HR = 0.88; 95% CI = 0.81-0.96; P = 0.003). High CD57⁺ TILs indicated a better OS in patients with EC (pooled HR = 0.50; 95% CI = 0.35-0.72; P < 0.001). In addition, the pooled results showed that other TIL subsets including CD3⁺, CD4⁺ and CD45RO⁺ TILs were not associated with patients’ survival (P > 0.05). Conclusions: For patients with EC, some TIL subsets could serve as prognostic biomarkers. The application of TILs in the immunotherapy of EC needs to be verified through a large amount of clinical research.

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“…In contrast to many cancers, HCCs do not generally down‐regulate HLA‐class I expression; HLA‐A is up‐regulated in 54% of patients . A recent meta‐analysis confirmed that high levels of HCC tumor infiltration by CD8 + T cells improved clinical outcomes, including overall survival . Several groups have isolated class I restricted tumor‐killing T‐cell clones that were generated spontaneously in HCC patients.…”

mentioning

confidence: 99%

Tuning T‐Cell Receptor Affinity to Optimize Clinical Risk‐Benefit When Targeting Alpha‐Fetoprotein–Positive Liver Cancer

et al. 2019

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Patients with hepatocellular carcinoma (HCC) have a poor prognosis and limited therapeutic options. Alpha‐fetoprotein (AFP) is often expressed at high levels in HCC and is an established clinical biomarker of the disease. Expression of AFP in nonmalignant liver can occur, particularly in a subset of progenitor cells and during chronic inflammation, at levels typically lower than in HCC. This cancer‐specific overexpression indicates that AFP may be a promising target for immunotherapy. We verified expression of AFP in normal and diseased tissue and generated an affinity‐optimized T‐cell receptor (TCR) with specificity to AFP/HLA‐A*02+ tumors. Expression of AFP was investigated using database searches, by qPCR, and by immunohistochemistry (IHC) analysis of a panel of human tissue samples, including normal, diseased, and malignant liver. Using in vitro mutagenesis and screening, we generated a TCR that recognizes the HLA‐A*02‐restricted AFP158‐166 peptide, FMNKFIYEI, with an optimum balance of potency and specificity. These properties were confirmed by an extension of the alanine scan (X‐scan) and testing TCR‐transduced T cells against normal and tumor cells covering a variety of tissues, cell types, and human leukocyte antigen (HLA) alleles. Conclusion: We have used a combination of physicochemical, in silico, and cell biology methods for optimizing a TCR for improved affinity and function, with properties that are expected to allow TCR‐transduced T cells to differentiate between antigen levels on nonmalignant and cancer cells. T cells transduced with this TCR constitute the basis for a trial of HCC adoptive T‐cell immunotherapy.

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The Prognostic Value of Tumor-infiltrating Lymphocytes in Hepatocellular Carcinoma: a Systematic Review and Meta-analysis

Cited by 118 publications

References 53 publications

Lymphocyte‐to‐Monocyte Ratio Is a Predictor of Survival After Liver Transplantation for Hepatocellular Carcinoma

Lymphocyte‐to‐Monocyte Ratio Is a Predictor of Survival After Liver Transplantation for Hepatocellular Carcinoma

Prognostic Role of Tumor-Infiltrating Lymphocytes in Esophagus Cancer: a Meta-Analysis

Tuning T‐Cell Receptor Affinity to Optimize Clinical Risk‐Benefit When Targeting Alpha‐Fetoprotein–Positive Liver Cancer

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