Expression pattern of cancer-associated fibroblast and its clinical relevance in intrahepatic cholangiocarcinoma

Zhang, Xiaofang; Dong, Min; Pan, Yuhang; Chen, Jianning; Huang, Xiaofeng; Jin, Y.; Shao, Chun-Kui

doi:10.1016/j.humpath.2017.04.014

Cited by 44 publications

(46 citation statements)

References 28 publications

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“…We categorized FTS into three tiers (immature vs. intermediate vs. mature), as previously proposed by Ueno et al in their study concerning rectal cancer, and found that immature FTS was an independent risk factor for both OS and RFS . These findings were in line with the previous study in ICC by Shao et al, in which the CAFs were dichotomized into “immature” and “mature” phenotypes . Furthermore, in two studies on PDAC, immature FTS was also found to have a negative impact on survival .…”

Section: Discussionsupporting

confidence: 84%

“…Taken together, the confusing discrepancies may in part lie in the material, because Fokas et al used tissue sections whereas Sinn et al used tissue microarrays. Beyond that, it is also noteworthy that the maturity of FTS has been reported to possess higher accuracy compared with α-SMA expression in prognosis stratification in both PDAC and ICC [12,17,22]. The molecular basis that supports the robust prognostic value of the maturity of FTS merits further study.…”

Section: © Alphamed Press 2018mentioning

confidence: 94%

“…On the other hand, recently, Shao et al summarized prognostic significances of a range of stroma‐derived biomarkers including α‐SMA expression and histological classification of CAFs in 71 ICC cases. Intriguingly, only their dichotomization on the morphological maturity of CAFs was identified as an independent prognostic factor for OS . However, the sample size was small, and they did not offer a way to apply their results in clinical practice.…”

Section: Introductionmentioning

confidence: 96%

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Prognostic Nomogram Based on Histological Characteristics of Fibrotic Tumor Stroma in Patients Who Underwent Curative Resection for Intrahepatic Cholangiocarcinoma

Jing

Huang

et al. 2018

The Oncologist

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Background Fibrotic tumor stroma (FTS) has been implicated in cancer promotion in several neoplasms. The histological features of FTS are convenient and easily accessible in clinical routine in intrahepatic cholangiocarcinoma (ICC) specimens. The goal of this study was to explore prognostic impacts of the quantity and maturity of FTS on surgical ICC patients. Moreover, we aimed to propose an efficient prognostic nomogram for postoperative ICC patients. Materials and Methods The clinical profiles of 154 consecutive postoperative ICC patients were retrospectively analyzed. Tumor‐stroma ratio and morphological maturity of FTS were evaluated on hematoxylin and eosin‐stained tumor sections. CD3, CD8, and α‐smooth muscle actin (α‐SMA) staining were performed on corresponding tissue microarrays. The nomogram was established on variables selected by multivariate analyses and was validated in 10‐fold cross‐validation. Results Rich tumor stroma and strong α‐SMA expression were associated with poor overall survival (OS). However, in multivariate analyses, these two biomarkers failed to stratify both OS and recurrence‐free survival (RFS). Immature FTS was correlated with tumor multiplicity, advanced clinical stage, and sparser CD3 and CD8 positive tumor‐infiltrating lymphocytes (TILs) and was identified as an independent prognostic indicator for both OS and RFS. The nomogram comprising FTS maturity, tumor number, microvascular invasion, and lymph node metastasis possessed higher predictive power relative to conventional staging systems. Conclusion Immature FTS was an independent risk factor for survival and was associated with sparser CD3 and CD8 positive TILs in ICC. The prognostic nomogram integrating the maturity of FTS offers a more accurate risk stratification for postoperative ICC patients. Implications for Practice Accumulating evidence has suggested that fibrotic components in tumor microenvironment (TME) play a complicated and vital role in TME reprogramming and cancer progression. However, in clinical practice, the evaluation of fibrotic tumor stroma (FTS) is still neglected to some extent. This study's findings indicated that, in intrahepatic cholangiocarcinoma (ICC), the histological maturity of FTS is a robust prognostic indicator for patients who underwent curative resection. Moreover, prognostic nomogram constructed on the maturity of FTS possessed higher predictive power relative to the conventional tumor‐node‐metastasis staging systems. Taken together, the evaluation of FTS should be emphasized in clinical routine for more accurate prognostic prediction in postoperative ICC patients.

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Section: Discussionsupporting

confidence: 84%

Section: © Alphamed Press 2018mentioning

confidence: 94%

Section: Introductionmentioning

confidence: 96%

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Prognostic Nomogram Based on Histological Characteristics of Fibrotic Tumor Stroma in Patients Who Underwent Curative Resection for Intrahepatic Cholangiocarcinoma

Jing

Huang

et al. 2018

The Oncologist

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“…In the tumoral milieu, CCA cells have been reported to be the main cellular component secreting PDGF-DD, which acts by binding to its receptor PDGFR-β expressed on CAFs, leading to their recruitment in the tumor site, together with other factors, such as TGFβ[ 150 , 151 ].…”

Section: Iccamentioning

confidence: 99%

“…Macrophages could be resident (KCs) or recruited from circulating monocytes via soluble factors, such as monocyte chemoattractant protein 1 (MCP-1/CCL2), released in the tumor milieu[ 151 , 164 ]. Once in the liver, they differentiate into tissue macrophages, acquiring specific subset and activation status according to the exposition of multiple signals in the TME[ 165 ].…”

Section: Iccamentioning

confidence: 99%

Tumor microenvironment in primary liver tumors: A challenging role of natural killer cells

Polidoro¹,

Mikulak²,

Cazzetta³

et al. 2020

WJG

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In the last years, several studies have been focused on elucidate the role of tumor microenvironment (TME) in cancer development and progression. Within TME, cells from adaptive and innate immune system are one of the main abundant components. The dynamic interactions between immune and cancer cells lead to the activation of complex molecular mechanisms that sustain tumor growth. This important cross-talk has been elucidate for several kind of tumors and occurs also in patients with liver cancer, such as hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA). Liver is well-known to be an important immunological organ with unique microenvironment. Here, in normal conditions, the rich immune-infiltrating cells cooperate with non-parenchymal cells, such as liver sinusoidal endothelial cells and Kupffer cells, favoring self-tolerance against gut antigens. The presence of underling liver immunosuppressive microenvironment highlights the importance to dissect the interaction between HCC and iCCA cells with immune infiltrating cells, in order to understand how this cross-talk promotes tumor growth. Deeper attention is, in fact, focused on immune-based therapy for these tumors, as promising approach to counteract the intrinsic anti-tumor activity of this microenvironment. In this review, we will examine the key pathways underlying TME cell-cell communications, with deeper focus on the role of natural killer cells in primary liver tumors, such as HCC and iCCA, as new opportunities for immune-based therapeutic strategies.

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Aging and biliary tract cancers: Epidemiology, molecular biology, and clinical practice

et al. 2022

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Biliary tract cancer (BTC) that contains cholangiocarcinoma, gallbladder cancer, and ampullary cancer is highly malignant and mostly diagnosed in elderly patients. Over the past decades, human life has globally risen; thus, aging emerges as the primary risk factor for BTC. However, an effective treatment for this vulnerable population remains a large clinical challenge. As a result, the incidence and mortality of TBC remains high. Here, we discuss the potential link between aging and BTC from the aspects of molecular and cellular mechanisms, surgical resection, and chemotherapy. In addition, we update a number of clinical trials that are currently ongoing in elderly patients. The overview of BTC in elderly patients is expected to help develop a new therapeutic strategy tailored to this elderly population, ultimately improving their life quality.

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Expression pattern of cancer-associated fibroblast and its clinical relevance in intrahepatic cholangiocarcinoma

Cited by 44 publications

References 28 publications

Prognostic Nomogram Based on Histological Characteristics of Fibrotic Tumor Stroma in Patients Who Underwent Curative Resection for Intrahepatic Cholangiocarcinoma

Prognostic Nomogram Based on Histological Characteristics of Fibrotic Tumor Stroma in Patients Who Underwent Curative Resection for Intrahepatic Cholangiocarcinoma

Tumor microenvironment in primary liver tumors: A challenging role of natural killer cells

Aging and biliary tract cancers: Epidemiology, molecular biology, and clinical practice

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