The Tumor Microenvironment in Cholangiocarcinoma Progression

Fabris, Luca; Sato, Keisaku; Alpini, Gianfranco; Strazzabosco, Mario

doi:10.1002/hep.31410

Cited by 141 publications

(105 citation statements)

References 88 publications

(100 reference statements)

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“…TME is the key regulator of carcinogenesis and consists of tumor cells, stromal cells, and immune cells (13,14). TICs are closely associated with tumorigenesis, angiogenesis and the growth and metastatic potential of tumor cells, which could alternately modulate the pattern of immune cells (15)(16)(17)(18). Now, immunotherapy has been widely used to treat a broad spectrum of cancers including BRCA (19)(20)(21)(22).…”

Section: Discussionmentioning

confidence: 99%

ATP2C2 Has Potential to Define Tumor Microenvironment in Breast Cancer

Liu

Wei

et al. 2021

Front. Immunol.

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Tumor microenvironment (TME) is vital for the occurrence and development of breast cancer (BRCA). However, it remains challenging to understand the dynamic modulation of the stromal and immune components comprehensively in TME. Herein, we used ESTIMATE and CIBERSORT algorithm to estimate the number of stromal and immune components and the abundance of tumor-infiltrating immune cells (TICs) in 582 BRCA cases from gene expression omnibus (GEO) database. We employed three regression models including univariable Cox proportion, LASSO regression model and multivariate Cox regression, and identified 7 immune-specific genes related to BRCA survival. Of 7 genes, ATPase Secretory Pathway Ca2+ Transporting 2 (ATP2C2) attracts our attention for significantly predicting prognosis of BRCA patients. Further analysis indicated that ATP2C2 expression was closely related to the clinicopathological features (age, T- and N-staging) and negatively correlated with patients’ survival in BRCA. Gene Set Enrichment Analysis (GSEA) was performed to reveal pathway enrichment between ATP2C2high and ATP2C2low groups. The low ATP2C2 expression groups’ genes were mainly enriched for immune-related activities, while those in the ATP2C2 high-expression group were largely enriched in metabolic-related pathways. Notably, Pearson’s correlation analysis identified that ATP2C2 expression was positively correlated with T follicular helper (Tfh) cells, and negatively correlated with gamma delta (γδ) T cell, suggesting that ATP2C2 might be accountable for the maintenance of immune-dominant status for TME. To sum up, this study comprehensively analyzed the TME and shed light on prognostic immune-related biomarkers for BRCA. In particular, ATP2C2 might be helpful for predicting the prognosis of BRCA patients, which provided an extra insight for BRCA treatment.

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Section: Discussionmentioning

confidence: 99%

ATP2C2 Has Potential to Define Tumor Microenvironment in Breast Cancer

Liu

Wei

et al. 2021

Front. Immunol.

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“…The tumor microenvironment (TME) represents another promising biomarker whose role as a predictor of the response to ICIs is under evaluation in several tumor types, with preclinical studies suggesting that TME could modify and modulate the host immune response against tumors [ 68 , 69 , 70 ]. As regards BTC, recent reports have highlighted that these hepatobiliary tumors are desmoplastic malignancies with the TME showing immunosuppressive innate immune cells, including tumor-associated macrophages and myeloid-derived suppressor cells [ 71 , 72 , 73 ]. In addition, the existence of distinct subgroups of tumors has been suggested, with immunologically “hot” and “cold” BTCs [ 74 ].…”

Section: Tmementioning

confidence: 99%

PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer

Rizzo

Ricci

Brandi

2021

Cancers

215

144

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Biliary tract cancer (BTC) represents the second most frequently diagnosed primary liver cancer worldwide following hepatocellular carcinoma, and the overall survival of patients with unresectable disease remains poor. In recent years, the advent of immune checkpoint inhibitors (ICIs) has revolutionized the therapeutic landscape of several malignancies with these agents, which have also been explored in advanced BTC, as monotherapy or in combination with other anticancer agents. However, clinical trials evaluating ICIs in BTC have shown conflicting results, and the clinical benefit provided by immunotherapy seems limited to a small subgroup of BTC patients. Thus, the identification of reliable predictors of the response to immunotherapy represents a significant challenge in this setting. This review provides an overview of the available evidence on the biomarkers predictive of the response to ICIs in patients with advanced BTC, especially focusing on programmed death-ligand 1 (PD-L1), tumor mutational burden (TMB), microsatellite instability (MSI), and other emerging biomarkers.

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“…Current evidence indicates that 53% intrahepatic cholangiocarcinoma harbor vascular endothelial growth factor (VEGF) overexpression which is related to poorer prognosis (10). Preclinical models appear to suggest that agents targeting VEGF, FEGF, EGFR and other signaling pathways can convert the tumor microenvironment and reprogram the immune responses to suppress tumorigenesis (11).…”

Section: Introductionmentioning

confidence: 99%

The Efficacy and Safety of Apatinib Plus Camrelizumab in Patients With Previously Treated Advanced Biliary Tract Cancer: A Prospective Clinical Study

Wang

Long

et al. 2021

Front. Oncol.

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BackgroundPD-1/L1 inhibitor-based immunotherapy is currently under investigation in biliary tract cancer (BTC). Apatinib combined with camrelizumab has achieved promising results in various tumor types. The aim of this study was to assess the safety and efficacy of apatinib plus camrelizumab for advanced biliary tract cancer patients who have received previously treatments.MethodsThis prospective, non-randomized, open-label trial was conducted at Peking Union Medical College Hospital (PUMCH). All included patients received apatinib orally at 250 mg per a day and camrelizumab intravenously at 200 mg every three weeks until disease progression or intolerable toxicity occurred. Efficacy was evaluated based on the Response Evaluation Criteria in Solid Tumors RECIST Version 1.1 (RECIST 1.1). Adverse events (AEs) were assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events (CTCAE version 4.0).ResultsA total of 22 patients were consecutively enrolled from 1st December, 2018 until 1st August, 2020. Among 21 patients for whom we could conduct efficacy evaluations, no patients achieved a complete response (CR), 4 patients (19%) achieved partial response (PR), and 11 patients had stable disease with a disease control rate of 71.4%. The median overall survival was 13.1 months (95% CI, 8.1-18.2), and the median progression-free survival was 4.4 months (95% CI, 2.4-6.3). All patients experienced treatment related AEs, and grade 3 or 4 AEs occurred in 14 (63.6%) of 22 patients. No treatment related deaths were observed.ConclusionsThis is the first report focusing on the efficacy and safety of camrelizumab plus apatinib in pretreated biliary tract cancer patients. The finding suggests this regimen has favorable therapeutic effects with relatively manageable toxicity. Further trials with a control arm are required to investigate.Clinical Trial Registrationidentifier NCT04642664.

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The Tumor Microenvironment in Cholangiocarcinoma Progression

Cited by 141 publications

References 88 publications

ATP2C2 Has Potential to Define Tumor Microenvironment in Breast Cancer

ATP2C2 Has Potential to Define Tumor Microenvironment in Breast Cancer

PD-L1, TMB, MSI, and Other Predictors of Response to Immune Checkpoint Inhibitors in Biliary Tract Cancer

The Efficacy and Safety of Apatinib Plus Camrelizumab in Patients With Previously Treated Advanced Biliary Tract Cancer: A Prospective Clinical Study

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