Inflammatory cells infiltrate and angiogenesis in locally advanced and metastatic cholangiocarcinoma

Tamma, Roberto; Annese, Tiziana; Ruggieri, Simona; Brunetti, Oronzo; Longo, Vito; Cascardi, Eliano; Mastropasqua, Mauro G.; Maiorano, Eugenio; Silvestris, Nicola; Ribatti, Doménico

doi:10.1111/eci.13087

Cited by 39 publications

(31 citation statements)

References 29 publications

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“…The development of potentially more effective anti-cancer agents, carriers for drug delivery, molecularly targeted drugs, and chemotherapy regimens followed by surgical treatment may improve outcomes for patient groups with poor prognoses, even when used in combination with current treatment strategies [29]. Furthermore, it has been reported that nutritional status is associated with the effects and outcomes of chemotherapy [30], and that inflammatory cells in the tumor microenvironment support tumor growth [31]; therefore, the maintenance of nutritional status and perioperative anti-inflammatory strategies may be important.…”

Section: Discussionmentioning

confidence: 99%

Examination of Prognostic Factors Affecting Long-Term Survival of Patients with Stage 3/4 Gallbladder Cancer without Distant Metastasis

Higuchi

Yazawa

Uemura

et al. 2020

Cancers

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In advanced gallbladder cancer (GBC) radical resection, if multiple prognostic factors are present, the outcome may be poor; however, the details remain unclear. To investigate the poor prognostic factors affecting long-term surgical outcome, we examined 157 cases of resected stage 3/4 GBC without distant metastasis between 1985 and 2017. Poor prognostic factors for overall survival and treatment outcomes of a number of predictable preoperative poor prognostic factors were evaluated. The surgical mortality was 4.5%. In multivariate analysis, blood loss, poor histology, liver invasion, and ≥4 regional lymph node metastases (LNMs) were independent prognostic factors for poor surgical outcomes; invasion of the left margin or the entire area of the hepatoduodenal ligament and a Clavien–Dindo classification ≥3 were marginal factors. The analysis identified outcomes of patients with factors that could be predicted preoperatively, such as liver invasion ≥5 mm, invasion of the left margin or the entire area of the hepatoduodenal ligament, and ≥4 regional LNMs. Thus, the five-year overall survival was 54% for zero factors, 34% for one factor, and 4% for two factors (p < 0.05). A poor surgical outcome was likely when two or more factors were predicted preoperatively; therefore, new treatment strategies are required for such patients.

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Section: Discussionmentioning

confidence: 99%

Examination of Prognostic Factors Affecting Long-Term Survival of Patients with Stage 3/4 Gallbladder Cancer without Distant Metastasis

Higuchi

Yazawa

Uemura

et al. 2020

Cancers

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“…Histopathologically, CCA is typified by an extensive cellular and acellular stroma that can comprise the bulk of the tumour 194 . CCA shares many characteristics with scars that form around bile ducts in premalignant disease, as usually found in PSC and congenital hepatic fibrosis, suggesting that the origin of the tumour stroma can be found in the regenerative microenvironment during bile duct repair 195 cells, CAFs and a complex group of inflammatory cells, including macrophages, neutrophils, natural killer (NK) and T cells 196 . In addition to this complex cellular microenvironment, the tumour stroma also contains an extensive network of ECM proteins such as collagens, laminin and fibronectin 197,198 .…”

Section: Chemoresistance and Survivalmentioning

confidence: 99%

Cholangiocarcinoma 2020: the next horizon in mechanisms and management

Bañales

Marin

Lamarca

et al. 2020

Nat Rev Gastroenterol Hepatol

1,512

1,562

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Cholangiocarcinoma (CCA) constitutes a diverse group of malignancies emerging in the biliary tree. CCAs are divided into three subtypes depending on their anatomical site of origin: intrahepatic (iCCA), perihilar (pCCA) and distal (dCCA) CCA 1,2 (Fig. 1). Of note, considered as an independent entity, mixed HCC-CCA tumours are a rare type of liver malignancy sharing features of both iCCA and HCC and presenting an aggressive disease course and poor prognosis 3,4. iCCAs arise above the second-order bile ducts, whereas the point of anatomical distinction between pCCA and dCCA is the insertion of the cystic duct. pCCA and dCCA can also be collectively referred to as 'extrahepatic' (eCCA) 5. In the USA, pCCA is the single largest group, accounting for approximately 50-60% of all CCAs, followed by dCCA (20-30%) and iCCA (10-20%) 1,6,7. CCA is the second most common primary hepatic malignancy after hepatocellular carcinoma (HCC), comprising approximately 15% of all primary liver tumours and 3% of gastrointestinal cancers 1,6,7. CCAs are usually asymptomatic in early stages and, therefore, often diagnosed when the disease is already in advanced stages, which highly compromises therapeutic options, resulting in a dismal prognosis 1,8. CCA is a rare cancer, but its incidence (0.3-6 per 100,000 inhabitants per year) 1 and mortality (1-6 per 100,000 inhabitants per year, globally 9 , not taking into account specific regions with incidence >6 per 100,000 habitants such as South Korea, China and Thailand) have been increasing in the past few decades worldwide, representing a global health problem. Despite advances in

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“…CD4+ and CD8+ T-cells represent the most significant anti-tumor cells [29,30]: CD8+ T-lymphocytes recognize specific tumor antigens such as MHC-I and exert anti-tumor activity in TME through the pro-inflammatory interferon-γ (IFN-γ) and granzymeperforin complex releases [31]; CD4+ T-lymphocytes are able to differentiate into specific effectors, including Thelper-1 (Th1)(secreting IL-2, IFN-γ and IFN-α which increase the anti-tumoral activity of macrophages and natural killer, NK, cells) [32] and T-helper-2 (Th2) (secreting IL-4, IL-5, IL-6, IL-10 and IL-13 which increase the pro-tumoral activity of macrophages) [32]. Effectively, TILs CD8+ and Th1 cytokines correlate with a favorable prognosis in many cancer types [33][34][35], whereas high levels of Treg cells in breast carcinomas are associated with an unfavorable prognosis [36][37][38]. Treg cells suppress T-cell activation [36], IFN-γ production [39] and the anti-tumor immune response.…”

Section: Tumor-infiltrating Lymphocytesmentioning

confidence: 99%

The Multifaceted Nature of Tumor Microenvironment in Breast Carcinomas

et al. 2020

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Heterogeneity in breast carcinomas can be appreciated at various levels, from morphology to molecular alterations, and there are well-known genotypic-phenotypic correlations. Clinical decision-making is strictly focused on the evaluation of tumor cells and is based on the assessment of hormone receptors and of the HER2 status, by means of a combination of immunohistochemical and in situ hybridization techniques. The tumor microenvironment (TME) also shows a multifaceted nature stemming from the different actors populating the intratumoral and the peritumoral stroma of breast carcinomas. Of note, we have now evidence that tumor-infiltrating lymphocytes (TILs) are clinically meaningful as their quantification in the intratumoral stroma strongly correlates with good prognosis, in particular in triple-negative and HER2-positive breast cancer patients. Nevertheless, TILs are just one of the many actors orchestrating the com-plexity of the TME, which is populated by immune and nonimmune cells (cancer-associated fibroblasts, cancer-associated adipocytes), as well as non-cellular components such as chemical inflammation mediators. In this review article we will overview the main features of the distinct cell compartments by discussing (i) the potential impact the TME may have on the prognostic stratification of breast cancers and (ii) the possible predictive value of some markers in the context of immunotherapy in light of the recent results of phase III studies in advanced and early triple-negative breast cancer patients.

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Inflammatory cells infiltrate and angiogenesis in locally advanced and metastatic cholangiocarcinoma

Cited by 39 publications

References 29 publications

Examination of Prognostic Factors Affecting Long-Term Survival of Patients with Stage 3/4 Gallbladder Cancer without Distant Metastasis

Examination of Prognostic Factors Affecting Long-Term Survival of Patients with Stage 3/4 Gallbladder Cancer without Distant Metastasis

Cholangiocarcinoma 2020: the next horizon in mechanisms and management

The Multifaceted Nature of Tumor Microenvironment in Breast Carcinomas

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