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Article ; Conference proceedings: Shift in cellular crosstalk reveals the immunosuppressive environment in cholangiocarcinoma patients

Heij, Lara R.

2024 Volume 62, Issue 01

Event/congress	40. Jahrestagung der Deutschen Arbeitsgemeinschaft zum Studium der Leber, Haus der Technik e.V., Essen, 2024-01-26
Language	German
Publishing date	2024-01-01
Publisher	Georg Thieme Verlag
Publishing place	Stuttgart ; New York
Document type	Article ; Conference proceedings
ZDB-ID	201387-3
ISSN	1439-7803 ; 0044-2771 ; 0172-8504
ISSN (online)	1439-7803
ISSN	0044-2771 ; 0172-8504
DOI	10.1055/s-0043-1777599
Database	Thieme publisher's database

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Zs.A 111: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 111/X: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article ; Conference proceedings: Nerve fibers in the tumor microenvironment as a novel biomarker in perihilar cholangiocarcinoma

Heij, Lara R. / Reichel, Konrad

Zeitschrift für Gastroenterologie

2024 Volume 62, Issue 01

Event/congress	40. Jahrestagung der Deutschen Arbeitsgemeinschaft zum Studium der Leber, Haus der Technik e.V., Essen, 2024-01-26
Language	German
Publishing date	2024-01-01
Publisher	Georg Thieme Verlag
Publishing place	Stuttgart ; New York
Document type	Article ; Conference proceedings
ZDB-ID	201387-3
ISSN	1439-7803 ; 0044-2771 ; 0172-8504
ISSN (online)	1439-7803
ISSN	0044-2771 ; 0172-8504
DOI	10.1055/s-0043-1777600
Database	Thieme publisher's database

In stock of ZB MED Cologne/Königswinter

Zs.A 111: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)
Zs.A 111/X: Show issues			Location: Je nach Verfügbarkeit (siehe Angabe bei Bestand) bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular Jg. 1995 - 2021: Lesesall (1.OG) ab Jg. 2022: Lesesaal (EG)

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Article: Editorial on "

Sivakumar, Shivan / Rocha, Flavio G / Heij, Lara

Hepatobiliary surgery and nutrition

2021 Volume 11, Issue 3, Page(s) 422–424

Language	English
Publishing date	2021-01-29
Publishing country	China (Republic : 1949- )
Document type	Editorial ; Comment
ZDB-ID	2812398-0
ISSN	2304-389X ; 2304-3881
ISSN (online)	2304-389X
ISSN	2304-3881
DOI	10.21037/hbsn-22-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: Identification and Validation of Potentially Clinically Relevant CpG Regions within the Class 2 Tumor Suppressor Gene

Hauschulz, Maximilian / Villwock, Sophia / Kosinski, Jennifer / Steib, Florian / Heij, Lara Rosaline / Bednarsch, Jan / Knüchel-Clarke, Ruth / Dahl, Edgar

Cancers

2023 Volume 15, Issue 3

Abstract: In pancreatic cancer treatment, tumor stage-dependent chemotherapies are used to prolong overall survival. By measuring DNA promoter hypermethylation in the plasma of patients with stage IV pancreatic cancer, it was recently shown that promoter DNA ... ...

Abstract	In pancreatic cancer treatment, tumor stage-dependent chemotherapies are used to prolong overall survival. By measuring DNA promoter hypermethylation in the plasma of patients with stage IV pancreatic cancer, it was recently shown that promoter DNA methylation of the tumor suppressor gene
Language	English
Publishing date	2023-01-22
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers15030683
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Increased risk of esophageal squamous cell carcinoma in patients with squamous dysplasia: a nationwide cohort study in the Netherlands.

van Tilburg, Laurelle / Spaander, Manon C W / Bruno, Marco J / Oudijk, Lindsey / Heij, Lara R / Doukas, Michail / Koch, Arjun D

Diseases of the esophagus : official journal of the International Society for Diseases of the Esophagus

2023 Volume 36, Issue 12

Abstract: Squamous dysplasia is the histological precursor of esophageal squamous cell carcinoma (ESCC). The optimal management for distinct squamous dysplasia grades remains unclear because the corresponding risk of developing ESCC is unknown. We aimed to assess ... ...

Abstract	Squamous dysplasia is the histological precursor of esophageal squamous cell carcinoma (ESCC). The optimal management for distinct squamous dysplasia grades remains unclear because the corresponding risk of developing ESCC is unknown. We aimed to assess the ESCC risk in patients with esophageal squamous dysplasia in a Western country. This nationwide cohort study included all patients with esophageal squamous dysplasia, diagnosed between 1991 and 2020 in the Dutch nationwide pathology databank (Palga). Squamous dysplasia was divided in mild-to-moderate dysplasia (mild, low-grade, and moderate dysplasia) and higher-grade dysplasia (high-grade dysplasia, severe dysplasia, carcinoma in situ). ESCC were identified in Palga and the Netherlands Cancer Registry. The primary endpoint was diagnosis of prevalent (≤6 months) and incident (>6 months after squamous dysplasia) ESCC. In total, 873 patients (55% male, aged 68 years SD ± 13.2) were diagnosed with esophageal squamous dysplasia, comprising mild-to-moderate dysplasia (n = 456), higher-grade dysplasia (n = 393), and dysplasia not otherwise specified (n = 24). ESCC was diagnosed in 77 (17%) patients with mild-to-moderate dysplasia (49 prevalent, 28 incident ESCC) and in 162 (41%) patients with higher-grade dysplasia (128 prevalent, 34 incident ESCC). After excluding prevalent ESCC, the annual risk of ESCC was 4.0% (95% CI: 2.7-5.7%) in patients with mild-to-moderate dysplasia and 8.5% (95% CI: 5.9-11.7%) in patients with higher-grade dysplasia. All patients with squamous dysplasia, including those with mild-to-moderate dysplasia, have a substantial risk of developing ESCC. Consequently, endoscopic surveillance of the esophageal mucosa or endoscopic resection of dysplasia should be considered for patients with mild-to-moderate dysplasia in Western countries. KEY MESSAGES What is already known on this topic? Squamous dysplasia is the histological precursor of ESCC and is divided in distinct grades, based on the proportion of the squamous epithelium with histopathological abnormalities. In Western countries, the optimal management for distinct squamous dysplasia grades remains unclear because the corresponding risk of developing ESCC is unknown. What this study adds The ESCC risk of patients with squamous dysplasia was increased for all patients with squamous dysplasia in a Western country; 2.1% for patients with mild dysplasia, 5.1% for low-grade dysplasia, and 5.2% for moderate dysplasia. Increasing grades of squamous dysplasia were associated with an increased ESCC risk. How this study might affect research, practice, or policy We recommend that endoscopic follow-up or treatment should be considered in all patients with esophageal squamous dysplasia in Western countries: 1) for patients with mild, low-grade, and moderate dysplasia, endoscopic surveillance with careful inspection with narrow band imaging or dye-based chromoendoscopy of the esophageal mucosa is indicated; and 2) for patients with high-grade dysplasia, severe dysplasia and carcinoma in situ adequate endoscopic staging and in case of suspected neoplasia endoscopic treatment should be performed.
MeSH term(s)	Humans ; Male ; Female ; Esophageal Squamous Cell Carcinoma/epidemiology ; Esophageal Neoplasms/epidemiology ; Esophageal Neoplasms/etiology ; Esophageal Neoplasms/diagnosis ; Carcinoma, Squamous Cell/pathology ; Cohort Studies ; Netherlands/epidemiology ; Esophagoscopy/methods ; Hyperplasia ; Carcinoma in Situ
Language	English
Publishing date	2023-07-30
Publishing country	United States
Document type	Journal Article
ZDB-ID	639470-x
ISSN	1442-2050 ; 1120-8694
ISSN (online)	1442-2050
ISSN	1120-8694
DOI	10.1093/dote/doad045
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Zs.A 2378: Show issues

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Je nach Verfügbarkeit (siehe Angabe bei Bestand)
bis Jg. 1994: Bestellungen von Artikeln über das Online-Bestellformular
Jg. 1995 - 2021: Lesesall (2.OG)
ab Jg. 2022: Lesesaal (EG)

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Article ; Online: Preoperative predictors for non-resectability in perihilar cholangiocarcinoma.

Otto, Carlos Constantin / Mantas, Anna / Heij, Lara Rosaline / Heise, Daniel / Dewulf, Maxime / Lang, Sven Arke / Ulmer, Tom Florian / Dahl, Edgar / Bruners, Philipp / Neumann, Ulf Peter / Bednarsch, Jan

World journal of surgical oncology

2024 Volume 22, Issue 1, Page(s) 48

Abstract: Introduction: Explorative laparotomy without subsequent curative-intent liver resection remains a major clinical problem in the treatment of perihilar cholangiocarcinoma (pCCA). Thus, we aimed to identify preoperative risk factors for non-resectability ... ...

Abstract	Introduction: Explorative laparotomy without subsequent curative-intent liver resection remains a major clinical problem in the treatment of perihilar cholangiocarcinoma (pCCA). Thus, we aimed to identify preoperative risk factors for non-resectability of pCCA patients. Material and methods: Patients undergoing surgical exploration between 2010 and 2022 were eligible for the analysis. Separate binary logistic regressions analyses were used to determine risk factors for non-resectability after explorative laparotomy due to technical (tumor extent, vessel infiltration) and oncological (peritoneal carcinomatosis, distant nodal or liver metastases)/liver function reasons. Results: This monocentric cohort comprised 318 patients with 209 (65.7%) being surgically resected and 109 (34.3%) being surgically explored [explorative laparotomy: 87 (27.4%), laparoscopic exploration: 22 (6.9%)]. The median age in the cohort was 69 years (range 60-75) and a majority had significant comorbidities with ASA-Score ≥ 3 (202/318, 63.5%). Statistically significant (p < 0.05) risk factors for non-resectability were age above 70 years (HR = 3.76, p = 0.003), portal vein embolization (PVE, HR = 5.73, p = 0.007), and arterial infiltration > 180° (HR = 8.05 p < 0.001) for technical non-resectability and PVE (HR = 4.67, p = 0.018), arterial infiltration > 180° (HR = 3.24, p = 0.015), and elevated CA 19-9 (HR = 3.2, p = 0.009) for oncological/liver-functional non-resectability. Conclusion: Advanced age, PVE, arterial infiltration, and elevated CA19-9 are major risk factors for non-resectability in pCCA. Preoperative assessment of those factors is crucial for better therapeutical pathways. Diagnostic laparoscopy, especially in high-risk situations, should be used to reduce the amount of explorative laparotomies without subsequent liver resection.
MeSH term(s)	Humans ; Middle Aged ; Aged ; Klatskin Tumor/surgery ; Klatskin Tumor/pathology ; Bile Duct Neoplasms/surgery ; Bile Duct Neoplasms/pathology ; Laparoscopy ; Hepatectomy ; Laparotomy ; Cholangiocarcinoma/surgery
Language	English
Publishing date	2024-02-07
Publishing country	England
Document type	Journal Article
ZDB-ID	2118383-1
ISSN	1477-7819 ; 1477-7819
ISSN (online)	1477-7819
ISSN	1477-7819
DOI	10.1186/s12957-024-03329-1
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Time to surgery is not an oncological risk factor in patients with cholangiocarcinoma undergoing curative-intent liver surgery.

Mantas, Anna / Liu, Dong / Otto, Carlos Constantin / Heij, Lara Rosaline / Heise, Daniel / Bruners, Philipp / Lang, Sven Arke / Ulmer, Tom Florian / Neumann, Ulf Peter / Bednarsch, Jan

Scientific reports

2024 Volume 14, Issue 1, Page(s) 1644

Abstract: Surgical resection is the only option to achieve long-term survival in cholangiocellular carcinoma (CCA). Due to limitations of health care systems and unforeseeable events, e.g., the COVID pandemic, the time from diagnosis to surgery (time-to-surgery ( ... ...

Abstract	Surgical resection is the only option to achieve long-term survival in cholangiocellular carcinoma (CCA). Due to limitations of health care systems and unforeseeable events, e.g., the COVID pandemic, the time from diagnosis to surgery (time-to-surgery (TTS)) has gained great interest in malignancies. Thus, we investigated whether TTS is associated with the oncological outcome in patients who underwent surgery for CCA. A cohort of 276 patients undergoing curative-intent surgery for intrahepatic and perihilar CCA excluding individuals with neoadjuvant therapy and perioperative mortality between 2010 and 2021 were eligible for analysis. Patients were grouped according to TTS (≤ 30; 31-60; 61-90; > 90 days) and compared by Kruskal-Wallis-analysis. Survival was compared using Kaplan-Meier analysis and characteristics associated with cancer-specific survival (CSS), recurrence-free survival (RFS) and overall survival (OS) using Cox regressions. The median CSS was 39 months (3-year-CSS = 52%, 5-year-CSS = 42%) and the median RFS 20 months (3-year-CSS = 38%, 5-year-CSS = 33%). In univariable Cox regressions, TTS was not associated with CSS (p = 0.971) or RFS (p = 0.855), respectively. A grouped analysis with respect to TTS (≤ 30 days, n = 106; 31-60 days, n = 134; 61-90 days, n = 44; > 90 days, n = 29) displayed a median CSS of 38, 33, 51 and 41 months and median RFS of 17, 22, 28 and 20 months (p = 0.971 log rank; p = 0.520 log rank). No statistical difference regarding oncological risk factors were observed between the groups. This study is the first comprehensive analysis of TTS in CCA patients. Within a representative European cohort, TTS was not associated with earlier tumor recurrence or reduced CCS.
MeSH term(s)	Humans ; Treatment Outcome ; Retrospective Studies ; Neoplasm Recurrence, Local ; Cholangiocarcinoma/pathology ; Liver/pathology ; Risk Factors ; Bile Ducts, Intrahepatic/pathology ; Bile Duct Neoplasms/pathology
Language	English
Publishing date	2024-01-18
Publishing country	England
Document type	Journal Article
ZDB-ID	2615211-3
ISSN	2045-2322 ; 2045-2322
ISSN (online)	2045-2322
ISSN	2045-2322
DOI	10.1038/s41598-023-50842-6
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: Body composition is associated with postoperative complications in perihilar cholangiocarcinoma.

Wang, Guanwu / Mantas, Anna / Heij, Lara R / Al-Masri, Tarick M / Liu, Dong / Heise, Daniel / Schmitz, Sophia M / Olde Damink, Steven W M / Luedde, Tom / Lang, Sven A / Ulmer, Tom F / Neumann, Ulf P / Bednarsch, Jan

Cancer medicine

2024

Abstract: Background: Perihilar cholangiocarcinoma (pCCA) is a malignant tumor of the hepatobiliary system which is still associated with a challenging prognosis. Postoperative complications play a crucial role in determining the overall prognosis of patients ... ...

Abstract	Background: Perihilar cholangiocarcinoma (pCCA) is a malignant tumor of the hepatobiliary system which is still associated with a challenging prognosis. Postoperative complications play a crucial role in determining the overall prognosis of patients with pCCA. Changes in body composition (BC) have been shown to impact the prognosis of various types of tumors. Therefore, our study aimed to investigate the correlation between BC, postoperative complications and oncological outcome in patients with pCCA. Methods: All patients with pCCA who underwent curative-intent surgery for pCCA between 2010 and 2022 were included in this analysis. BC was assessed using preoperative computed tomography and analyzed with the assistance of a 3D Slicer software. Univariate and multivariate binary logistic regression analyses were conducted to examine the relationship between BC and clinical characteristics including various measurements of postoperative complications and Cox regressions and Kaplan-Meier analysis to evaluate oncological risk factors in the study cohort. Results: BC was frequently altered in patients undergoing curative-intent liver resection for pCCA (n = 204) with 52.5% of the patients showing obesity, 55.9% sarcopenia, 21.6% sarcopenic obesity, 48.5% myosteatosis, and 69.1% visceral obesity. In multivariate analysis, severe postoperative complications (Clavien-Dindo ≥3b) were associated with body mass index (BMI) (Odds ratio (OR) = 2.001, p = 0.024), sarcopenia (OR = 2.145, p = 0.034), and myosteatosis (OR = 2.097, p = 0.017) as independent predictors. Furthermore, sarcopenia was associated with reduced overall survival (OS) in pCCA patients (sarcopenia vs. no-sarcopenia, 21 months vs. 32 months, p = 0.048 log rank). Conclusions: BC is highly associated with severe postoperative complications in patients with pCCA and shows tendency to be associated impaired overall survival. Preoperative assessment of BC and interventions to improve BC might therefore be key to improve outcome in pCCA patients undergoing surgical therapy.
Language	English
Publishing date	2024-01-01
Publishing country	United States
Document type	Journal Article
ZDB-ID	2659751-2
ISSN	2045-7634 ; 2045-7634
ISSN (online)	2045-7634
ISSN	2045-7634
DOI	10.1002/cam4.6878
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article: The Role of Single-Nucleotide Polymorphisms in Cholangiocarcinoma: A Systematic Review.

Wang, Guanwu / Heij, Lara Rosaline / Liu, Dong / Dahl, Edgar / Lang, Sven Arke / Ulmer, Tom Florian / Luedde, Tom / Neumann, Ulf Peter / Bednarsch, Jan

Cancers

2022 Volume 14, Issue 23

Abstract: Single-nucleotide polymorphisms (SNPs) play an essential role in various malignancies, but their role in cholangiocarcinoma (CCA) remains to be elucidated. Therefore, the purpose of this systematic review was to evaluate the association between SNPs and ... ...

Abstract	Single-nucleotide polymorphisms (SNPs) play an essential role in various malignancies, but their role in cholangiocarcinoma (CCA) remains to be elucidated. Therefore, the purpose of this systematic review was to evaluate the association between SNPs and CCA, focusing on tumorigenesis and prognosis. A systematic literature search was carried out using PubMed, Embase, Web of Science and the Cochrane database for the association between SNPs and CCA, including literature published between January 2000 and April 2022. This systematic review compiles 43 SNPs in 32 genes associated with CCA risk, metastatic progression and overall prognosis based on 34 studies. Susceptibility to CCA was associated with SNPs in genes related to inflammation (PTGS2/COX2, IL6, IFNG/IFN-γ, TNF/TNF-α), DNA repair (ERCC1, MTHFR, MUTYH, XRCC1, OGG1), detoxification (NAT1, NAT2 and ABCC2), enzymes (SERPINA1, GSTO1, APOBEC3A, APOBEC3B), RNA (HOTAIR) and membrane-based proteins (EGFR, GAB1, KLRK1/NKG2D). Overall oncological prognosis was also related to SNPs in eight genes (GNB3, NFE2L2/NRF2, GALNT14, EGFR, XRCC1, EZH2, GNAS, CXCR1). Our findings indicate that multiple SNPs play different roles at various stages of CCA and might serve as biomarkers guiding treatment and allowing oncological risk assessment. Considering the differences in SNP detection methods, patient ethnicity and corresponding environmental factors, more large-scale multicentric investigations are needed to fully determine the potential of SNP analysis for CCA susceptibility prediction and prognostication.
Language	English
Publishing date	2022-12-02
Publishing country	Switzerland
Document type	Journal Article ; Review
ZDB-ID	2527080-1
ISSN	2072-6694
ISSN	2072-6694
DOI	10.3390/cancers14235969
Database	MEDical Literature Analysis and Retrieval System OnLINE

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Article ; Online: The role of tumor-infiltrating lymphocytes in cholangiocarcinoma.

Liu, Dong / Heij, Lara Rosaline / Czigany, Zoltan / Dahl, Edgar / Lang, Sven Arke / Ulmer, Tom Florian / Luedde, Tom / Neumann, Ulf Peter / Bednarsch, Jan

Journal of experimental & clinical cancer research : CR

2022 Volume 41, Issue 1, Page(s) 127

Abstract: Cholangiocarcinoma (CCA) is the second most common primary liver cancer and associated with a dismal prognosis due to the lack of an efficient systemic therapy. In contrast to other cancers, new immunotherapies have demonstrated unsatisfactory results in ...

Abstract	Cholangiocarcinoma (CCA) is the second most common primary liver cancer and associated with a dismal prognosis due to the lack of an efficient systemic therapy. In contrast to other cancers, new immunotherapies have demonstrated unsatisfactory results in clinical trials, underlining the importance of a deeper understanding of the special tumor microenvironment of CCA and the role of immune cells interacting with the tumor. Tumor-infiltrating lymphocytes (TILs) are an important component of the adaptive immune system and the foundation of current immunotherapy. Therefore, the aim of this systemic review is to summarize the current literature focusing on the proportions and distribution, molecular pathogenesis, prognostic significance of TILs and their role in immunotherapy for CCA patients.In CCA, CD8+ and CD4+ T lymphocytes represent the majority of TILs and are mostly sequestered around the cancer cells. CD20+ B lymphocytes and Natural Killer (NK) cells are less frequent. In contrast, Foxp3+ cells (regulatory T cells, Tregs) are observed to infiltrate into the tumor. In the immune microenvironment of CCA, cancer cells and stromal cells such as TAMs, TANs, MSDCs and CAFs inhibit the immune protection function of TILs by secreting factors like IL-10 and TGF-β. With respect to molecular pathogenesis, the Wnt/-catenin, TGF-signaling routes, aPKC-i/P-Sp1/Snail Signaling, B7-H1/PD-1Pathway and Fas/FasL signaling pathways are connected to the malignant potential and contributed to tumor immune evasion by increasing TIL apoptosis. Distinct subtypes of TILs show different prognostic implications for the long-term outcome in CCA. Although there are occasionally conflicting results, CD8+ and CD4+ T cells, and CD20+ B cells are positively correlated with the oncological prognosis of CCA, while a high number of Tregs is very likely associated with worse overall survival. TILs also play a major role in immunotherapy for CCA.In summary, the presence of TILs may represent an important marker for the prognosis and a potential target for novel therapy, but more clinical and translationaldata is needed to fully unravel the importance of TILs in the treatment of CCA.
MeSH term(s)	B7-H1 Antigen/metabolism ; Bile Duct Neoplasms/pathology ; Bile Duct Neoplasms/therapy ; Bile Ducts, Intrahepatic/metabolism ; Bile Ducts, Intrahepatic/pathology ; CD8-Positive T-Lymphocytes ; Cholangiocarcinoma/pathology ; Humans ; Immunotherapy/methods ; Lymphocytes, Tumor-Infiltrating ; Prognosis ; Tumor Microenvironment
Chemical Substances	B7-H1 Antigen
Language	English
Publishing date	2022-04-07
Publishing country	England
Document type	Journal Article ; Review
ZDB-ID	803138-1
ISSN	1756-9966 ; 0392-9078
ISSN (online)	1756-9966
ISSN	0392-9078
DOI	10.1186/s13046-022-02340-2
Database	MEDical Literature Analysis and Retrieval System OnLINE

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