Prognostic impact of CD8+ T cell distribution and its association with the HLA class I expression in intrahepatic cholangiocarcinoma

Asahi, Yoh; Hatanaka, Kanako C.; Hatanaka, Yutaka; Kamiyama, Toshiya; Orimo, Tatsuya; Shimada, Shingo; Nagatsu, Akito; Sakamoto, Yuzuru; Kamachi, Hirofumi; Kobayashi, Nozomi; Fukai, Moto; Taketomi, Akinobu

doi:10.1007/s00595-020-01967-y

Cited by 38 publications

(43 citation statements)

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“…However, there has been some controversy in previous studies regarding the effect of PD-L1 + expression on the prognosis of ICC. [20][21][22][23][24][25][26] The present findings showed a significant relationship between PD-L1 + expression and poor outcomes in ICC patients since the PD-1/PD-L1 pathway contributes to malignant potential and immune tolerance in ICC. 27 These contradictory results may be related to the use of different antibodies and cut-off values.…”

Section: Discussionsupporting

confidence: 55%

Machine learning: an approach to preoperatively predict PD-1/PD-L1 expression and outcome in intrahepatic cholangiocarcinoma using MRI biomarkers

Zhang

Zhang³

et al. 2020

ESMO Open

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ObjectiveTo investigate the preoperative predictive value of non-invasive imaging biomarkers for programmed cell death protein 1/programmed cell death protein ligand 1 (PD-1/PD-L1) expression and outcome in intrahepatic cholangiocarcinoma (ICC) using machine learning.MethodsPD-1/PD-L1 expression in 98 ICC patients was assessed by immunohistochemistry, and their prognostic effects were analysed using Cox regression and Kaplan-Meier analysis. Radiomic features were extracted from MRI in the arterial and portal vein phases, and three sets of Radiomics score (Radscore) with good performance were derived respectively as biomarkers for predicting PD-1, PD-L1 expression and overall survival (OS). PD-1 and PD-L1 expression models were developed using the Radscore (arterial phase), clinico-radiological factors and clinical factors, individually and in combination. The imaging-based OS predictive model was constructed by combining independent predictors among clinico-radiological, clinical factors and OS Radscore. Pathology-based OS model using pathological and clinical factors was also constructed and compared with imaging-based OS model.ResultsThe highest area under the curves of the models predicting PD-1 and PD-L1 expression was 0.897 and 0.890, respectively. PD-1+ and PD-L1+ cases had worse outcomes than negative cases. The 5-year survival rates of PD-1+ and PD-1− cases were 12.5% and 48.3%, respectively (p<0.05), whereas the 5-year survival was 21.9% and 39.4% for PD-L1+ and PD-L1− cases, respectively (p<0.05). The imaging-based OS model involved predictors of clinico-radiological ‘imaging classification’, radiomics ‘Radscore’ from arterial phase and carcinoembryonic antigen (CEA) level (C-index:0.721). It performed better than pathology-based model (C-index: 0.698) constructed by PD-1/PD-L1 expression status and CEA level. The imaging-based OS model is potential for practice when the pathology assay is unavailable and could divide ICC patients into high-risk and low-risk groups, with 1-year, 3-year and 5-year survival rates of 57.1%, 14.3% and 12.4%, and 87.8%, 63.3% and 55.3%, respectively (p<0.001).ConclusionsMRI radiomics could derive promising and non-invasive biomarker in evaluating PD-1/PD-L1 expression and prognosis of ICC patients.

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Section: Discussionsupporting

confidence: 55%

Machine learning: an approach to preoperatively predict PD-1/PD-L1 expression and outcome in intrahepatic cholangiocarcinoma using MRI biomarkers

Zhang

Zhang³

et al. 2020

ESMO Open

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“…TILs include various types of lymphocytes, such as CD3 + , CD4 + , CD8 + cells; CD8 + T cells are considered especially important among them. Tumor in ltration by CD8 + T cells has been strongly associated with survival of cancer patients [26,28]. Yoshida et al also reported that CRP inhibited proliferation, activation, and function of CD8 + T cells in patients with melanoma [40].…”

Section: Discussionmentioning

confidence: 99%

Prognostic implications of lymphocyte/C-reactive protein ratio with tumor-infiltrating lymphocytes in resected intrahepatic cholangiocarcinoma

Miyazaki

Morine

Imura

et al. 2020

Preprint

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Background Lymphocyte/C-reactive protein (CRP) ratio (LCR), is a promising prognostic factor that can reflect tumor inflammation and systemic patient condition. The aim of this study was to investigate whether preoperative LCR can be a prognostic factor for post-surgical outcomes among patients with intrahepatic cholangiocarcinoma (IHCC). We also investigated the relationship between LCR and tumor infiltrating lymphocytes (TILs) to clarify whether systemic host immune parameters reflect local tumor immunity.Methods We enrolled 45 patients who had undergone hepatectomy for IHCC. Patients were divided into low LCR and high LCR groups, according to reactive operating characteristic curve (Cut-off value: 8780). We analyzed their overall survival (OS) and disease-free survival (DFS) with respect to LCR and other clinicopathological factors. We also investigated stromal TILs and numbers of CD8+ TILs in surgical specimens, and the relationship between LCR and TILs.Results Twenty-one patients (46.7%) were associated with low LCR. Low LCR was significantly correlated with older age, high CRP and advanced disease stage, and was a prognostic factor for OS and DFS. And multivariate analysis revealed that low LCR was an independent prognostic factor for worse OS (HR: 2.81 P<0.04). Regarding the relationship between LCR and local tumor immunity, while LCR and levels for stromal TILs were significantly related, LCR and levels for CD8+ TILs were significantly related. Conclusions Preoperative LCR levels could predict the post-surgical prognosis of patients with IHCC, and reflected numbers of intra-tumoral CD8+ TILs.Trial registration This study was approved by Tokushima University Hospital ethics committee and with the approval of corresponding regulatory agencies, and all the experiments were carried out in accordance with the approved guidelines (Tokushima Clinical Trial Management System Number; 3215). All the patients involved in this study signed informed consent forms and agreed to participate.

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“…It is known that tumors often downregulate the expression of human leukocyte antigen (HLA) as a mechanism of the evasion from immune recognition and destruction by T cells [44]. However, contradictory results have been obtained in different cohorts of iCCA and eCCA, ranging from the description of high expression of HLA-I on tumor cells [45] to those with only 40-50% of HLA-I-positive tumors [46,47]. Nevertheless, regardless of the analyzed cohort, CD8 + T cells that infiltrate tumor zones have the greatest capacity to induce a tumor cell death.…”

Section: T and B Cells In Ccamentioning

confidence: 99%

Molecular and Immunological Characterization of Biliary Tract Cancers: A Paradigm Shift Towards a Personalized Medicine

Malenica

Donadon

Lleo

2020

Cancers

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Biliary tract cancers (BTCs) are a group of rare cancers that account for up to 3–5% of cancer patients worldwide. BTCs include cholangiocarcinoma (CCA), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). They are frequently diagnosed at an advanced stage when the disease is often found disseminated. A late diagnosis highly compromises surgery, the only potentially curative option. Current treatment regimens include a combination of chemotherapeutic drugs gemcitabine with cisplatin that have a limited efficiency since more than 50% of patients relapse in the first year. More recently, an inhibitor of fibroblast growth factor receptor 2 (FGFR2) was approved as a second-line treatment, based on the promising results from the NCT02924376 clinical trial. However, novel secondary treatment options are urgently needed. Recent molecular characterization of CCA and GBC highlighted the molecular heterogeneity, etiology, and epidemiology in BTC development and lead to the classification of the extrahepatic CCA into four types: metabolic, proliferating, mesenchymal, and immune type. Differences in the immune infiltration and tumor microenvironment (TME) have been described as well, showing that only a small subset of BTCs could be classified as an immune “hot” and targeted with the immunotherapeutic drugs. This recent evidence has opened a way to new clinical trials for BTCs, and new drug approvals are highly expected by the medical community.

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Prognostic impact of CD8+ T cell distribution and its association with the HLA class I expression in intrahepatic cholangiocarcinoma

Cited by 38 publications

References 47 publications

Machine learning: an approach to preoperatively predict PD-1/PD-L1 expression and outcome in intrahepatic cholangiocarcinoma using MRI biomarkers

Machine learning: an approach to preoperatively predict PD-1/PD-L1 expression and outcome in intrahepatic cholangiocarcinoma using MRI biomarkers

Prognostic implications of lymphocyte/C-reactive protein ratio with tumor-infiltrating lymphocytes in resected intrahepatic cholangiocarcinoma

Molecular and Immunological Characterization of Biliary Tract Cancers: A Paradigm Shift Towards a Personalized Medicine

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