Prognostic role and clinicopathological features of SMAD4 gene mutation in colorectal cancer: a systematic review and meta-analysis

Abstract Background Approximately 5.0–24.2% of colorectal cancers (CRCs) have inactivating mutations in SMAD4, making it one of the frequently mutated genes in CRC. We thus carried out a comprehensive system review and meta-analysis investigating the prognostic significance and clinicopathological features of SMAD4 gene mutation in CRC patients. Methods A detailed literature search was conducted in PubMed, Web of Science and Embase databases to study the relationship between SMAD4 mutations and the demographic and clinicopathological characteristics in CRC patients. The hazard ratios (HRs) with 95% confidence intervals (CI) were used to evaluate the effect of SMAD4 mutations on overall survival (OS) and progression-free survival (PFS)/recurrence-free survival (RFS). Results Ten studies enrolling 4394 patients were eligible for inclusion. Data on OS were available from 5 studies and data on PFS/RFS were available from 3 studies. Comparing SMAD4-mutated CRC patients with SMAD4 wild-type CRC patients, the summary HR for OS was 1.46 (95% CI 1.28–1.67, P = 0.001), the summary HR for PFS/RFS was 1.59 (95% CI 1.14–2.22, P = 0.006). In terms of clinicopathology parameters, 9 studies have data that can be extracted, SMAD4 mutations were associated with tumor location (odds ratio [OR] = 1.15, colon/rectum, 95% CI 1.01–1.31, P = 0.042), TNM stage (OR = 1.28, stage IV/I–III, 95% CI 1.03–1.58, P = 0.025), lymph node metastasis (OR = 1.42, N1 + N2/N0, 95% CI 1.20–1.67, P < 0.001), mucinous differentiation (OR = 2.23, 95% CI 1.85–2.70, P < 0.001) and rat sarcoma viral oncogene homolog (RAS) mutation status (OR = 2.13, 95% CI 1.37–3.34, P = 0.001). No connection was found with age, gender, tumor grade, microsatellite instability status and b-viral oncogene homolog B1 mutation status. Besides, publication bias was not observed in any study. Conclusions This meta-analysis suggests that SMAD4 mutation was associated with OS, PFS/RFS, and clinicopathological parameters, including tumor site, disease stage, RAS status, lymph node metastasis and mucinous differentiation. Our meta-analysis indicated that SMAD4 mutations could predict the poor prognosis and aggressive clinicopathological characteristics of CRC. More large-sample cohort studies are needed to confirm this conclusion. Since SMAD4 mutations are closely related to RAS mutations, their relationship warrants further investigation.

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Prognostic role and clinicopathological features of SMAD4 gene mutation in colorectal cancer: a systematic review and meta-analysis

10.21203/rs.3.rs-379114/v1 ◽

2021 ◽

Author(s):

Tian Fang ◽

Tingting Liang ◽

Yizhuo Wang ◽

Chang Wang

Keyword(s):

Lymph Node ◽

Meta Analysis ◽

Clinicopathological Characteristics ◽

Clinicopathological Features ◽

Wild Type ◽

Free Survival ◽

Smad4 Gene ◽

Node Metastases ◽

Viral Oncogene Homolog ◽

Smad4 Mutation

Abstract Background Approximately 5.0%-24.2% of colorectal cancers (CRCs) have activating mutations in SMAD4, making it one of the frequently mutated genes in CRC. We thus carried out a comprehensive system review and meta-analysis investigating the prognostic significance and clinicopathological features of mutation of SMAD4 gene in CRC. Methods A detailed literature search was conducted in PubMed, Web of Science and Embase databases to study the relationship between mutations of SMAD4 gene and the demographic and clinicopathological characteristics in patients with CRC. The hazard ratios with 95% confidence intervals were used to evaluate the effect of SMAD4 mutations on overall survival (OS) and progression-free survival (PFS)/recurrence-free survival (RFS).Results Ten studies enrolling 4394 patients were eligible for inclusion. Data on OS were available from five studies. Comparing SMAD4-mutated CRC patients with SMAD4 wild-type CRC patients, the summary HR for OS was 1.46 (95% confidence interval [95% CI] 1.28–1.67, P=0.001), the summary HR for PFS/RFS was 1.59 (95% CI=1.14–2.22, P=0.006). In terms of clinicopathology parameters, SMAD4 mutations were associated with tumor location (odds ratio [OR]= 1.15, colon/rectum, 95% CI=1.01-1.31, P=0.042), TNM stage (OR=0.78, stage Ⅰ-Ⅲ/Ⅳ, [95% CI] 0.63-0.97, P=0.025), lymph node metastases (OR=1.42, N+/N0, 95% CI=1.20-1.67, P<0.001), mucinous differentiation (OR=2.23, 95% CI=1.85-2.70, P<0.001) and rat sarcoma viral oncogene homolog (RAS) status (OR=0.47, RAS wild-type/RAS mutation, 95% CI=0.30-0.73, P=0.001). No connection was found with age, gender, tumor grade, microsatellite instability (MSI) status and b-viral oncogene homolog B1(BRAF) status. Besides, publication bias was not observed in all studies.Conclusions This meta-analysis suggests that SMAD4 mutation was associated with OS, PFS/RFS, and clinicopathological parameters, including tumor site, disease stage, RAS status, lymph node metastases and tumor mucinous differentiation. It was indicated that SMAD4 mutations could predict the poor prognosis and aggressive clinicopathological characteristics of CRC. More large-sample cohort studies were needed to further confirm this conclusion. As SMAD4 mutation was found to be closely associated with RAS mutations, their relationship was worth further investigating.

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Impact of S100A4 Expression on Clinicopathological Characteristics and Prognosis in Pancreatic Cancer: A Meta-Analysis

Disease Markers ◽

10.1155/2016/8137378 ◽

2016 ◽

Vol 2016 ◽

pp. 1-9 ◽

Cited By ~ 9

Author(s):

Shanshan Huang ◽

Jiawei Zheng ◽

Yufang Huang ◽

Li Song ◽

Yin Yin ◽

...

Keyword(s):

Pancreatic Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Meta Analysis ◽

Clinicopathological Characteristics ◽

Node Metastasis ◽

Relative Risks ◽

Potential Marker ◽

S100a4 Expression ◽

The Relationship

Background.The small Ca2+-binding protein S100A4 is identified as a metastasis-associated or metastasis-inducing protein in various types of cancer. The goal of this meta-analysis was to evaluate the relationship between S100A4 expression and clinicopathological characteristics and prognosis of patients with pancreatic cancer.Methods. A comprehensive literature search was carried out in the electronic databases PubMed and Chinese CNKI. Only the studies reporting the correlation between S100A4 expression and clinicopathological characteristics or overall survival (OS) of patients with pancreatic cancer are enrolled. Extracted data was analyzed using the RevMan 5.3 software to calculate the pooled relative risks (95% confidence interval, CI) for statistical analyses.Results.Seven studies including a total of 474 patients were enrolled into this meta-analysis. Negative expression of S100A4 was significantly associated with higher 3-year OS rate (RR = 3.92, 95% CI = 2.24–6.87,P<0.0001), compared to S100A4-positive cases. Moreover, negative expression of S100A4 was also related to N0 stage for lymph node metastasis (RR = 2.15, 95% CI = 1.60–2.88,P<0.0001). However, S100A4 expression was not significantly correlated with histological types and distant metastasis status.Conclusion.S100A4 expression represents a potential marker for lymph node metastasis of pancreatic cancer and a potential unfavorable factor for prognosis of patients with this disease.

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SPARCL1, a Novel Prognostic Predictive Factor for GI Malignancies: a Meta-Analysis

Cellular Physiology and Biochemistry ◽

10.1159/000485584 ◽

2017 ◽

Vol 44 (4) ◽

pp. 1485-1496 ◽

Cited By ~ 4

Author(s):

Hanguang Hu ◽

Wen Cai ◽

Shu Zheng ◽

Weiting Ge

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Publication Bias ◽

Predictive Factor ◽

Meta Analysis ◽

Experimental Studies ◽

Clinicopathological Features ◽

Cancer Type ◽

Tumor Differentiation ◽

Node Metastasis

Background/Aims: Secreted protein acidic and rich in cysteines-like 1 (SPARCL1) is abnormally expressed in gastrointestinal (GI) malignancies. However, the correlation between SPARCL1 expression and the prognosis of patients remains unknown. Therefore, we performed a meta-analysis to investigate the potential value of SPARCL1 as a prognostic predictive marker for GI malignancies. Methods: The PubMed, Embase, EBSCO, CNKI, and Wanfang databases were systematically searched for studies examining SPARCL1 and clinicopathological features, including the prognoses of patients. Hazard ratios (HRs) and odds ratios (ORs) from individual studies were calculated and pooled using a random-effects or fix-effects model. Heterogeneity and publication bias analyses were performed. Results: Data from 8 studies, including a total of 2,356 patients, were summarized. The expression of SPARCL1 suggested a better prognosis (HR=0.57, 95% CI: 0.445-0.698, P=0.000) and was associated with clinicopathological features of GI malignancies, including distant metastasis (OR=0.44, 95% CI: 0.23-0.85, P=0.014), lymph node metastasis (OR=0.56, 95% CI: 0.39–0.81, P=0.002) and tumor differentiation (OR=2.21, 95% CI: 1.82–2.69, P=0.000). Subgroup analyses based on cancer type revealed that the expression of SPARCL1 had no effect on lymph node metastasis in colorectal cancer, and it did not influence tumor differentiation in gastric cancer. Egger’s test showed no evidence of publication bias (all P>0.05). Conclusion: SPARCL1 could be a novel prognostic predictive factor for GI malignancies. The expression of SPARCL1 could influence the clinicopathological features of GI malignancies. Further large-scale studies are essential to confirm SPARCL1’s prognostic predictive value, and more fundamental experimental studies are needed to illustrate the mechanisms.

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Association of Myometrial Invasion With Lymphovascular Space Invasion, Lymph Node Metastasis, Recurrence, and Overall Survival in Endometrial Cancer: A Meta-Analysis of 79 Studies With 68,870 Patients

Frontiers in Oncology ◽

10.3389/fonc.2021.762329 ◽

2021 ◽

Vol 11 ◽

Author(s):

Jianzhang Wang ◽

Ping Xu ◽

Xueying Yang ◽

Qin Yu ◽

Xinxin Xu ◽

...

Keyword(s):

Overall Survival ◽

Endometrial Cancer ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Meta Analysis ◽

Myometrial Invasion ◽

Clinicopathological Characteristics ◽

Node Metastasis ◽

Deep Myometrial Invasion ◽

Lymphovascular Space Invasion

BackgroundMyometrial invasion has been demonstrated to correlate to clinicopathological characteristics and prognosis in endometrial cancer. However, not all the studies have the consistent results and no meta-analysis has investigated the association of myometrial invasion with lymphovascular space invasion (LVSI), lymph node metastasis (LNM), recurrence, and overall survival (OS). Therefore, a meta-analysis was performed to evaluate the relationship between myometrial invasion and clinicopathological characteristics or overall survival in endometrial cancer.Materials and MethodsA search of Pubmed, Embase, and Web of Science was carried out to collect relevant studies from their inception until June 30, 2021. The quality of each included study was evaluated using Newcastle–Ottawa scale (NOS) scale. Review Manager version 5.4 was employed to conduct the meta-analysis.ResultsA total of 79 articles with 68,870 endometrial cancer patients were eligible including 9 articles for LVSI, 29 articles for LNM, 8 for recurrence, and 37 for OS in this meta-analysis. Myometrial invasion was associated with LVSI (RR 3.07; 95% CI 2.17–4.35; p < 0.00001), lymph node metastasis (LNM) (RR 4.45; 95% CI 3.29–6.01; p < 0.00001), and recurrence (RR 2.06; 95% CI 1.58–2.69; p < 0.00001). Deep myometrial invasion was also significantly related with poor OS via meta-synthesis of HRs in both univariate survival (HR 3.36, 95% CI 2.35–4.79, p < 0.00001) and multivariate survival (HR 2.00, 95% CI 1.59–2.53, p < 0.00001). Funnel plot suggested that there was no significant publication bias in this study.ConclusionDeep myometrial invasion correlated to positive LVSI, positive LNM, cancer recurrence, and poor OS for endometrial cancer patients, indicating that myometrial invasion was a useful evaluation criterion to associate with clinical outcomes and prognosis of endometrial cancer since depth of myometrial invasion can be assessed before surgery. The large scale and comprehensive meta-analysis suggested that we should pay more attention to myometrial invasion in clinical practice, and its underlying mechanism also deserves further investigation.

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Association between LKB1 expression and prognosis of patients with solid tumours: an updated systematic review and meta-analysis

BMJ Open ◽

10.1136/bmjopen-2018-027185 ◽

2019 ◽

Vol 9 (8) ◽

pp. e027185 ◽

Cited By ~ 1

Author(s):

Yun Hong Ren ◽

Feng Juan Zhao ◽

Han Yue Mo ◽

Rong Rong Jia ◽

Juan Tang ◽

...

Keyword(s):

Systematic Review ◽

Multivariate Analysis ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Meta Analysis ◽

Univariate Analysis ◽

Solid Tumours ◽

Free Survival ◽

Node Metastasis ◽

Tumour Differentiation

ObjectivesLiver kinase B1 (LKB1) is considered a tumour suppressor that can control cell growth and metabolism. Whether LKB1 expression levels are related to clinicopathology and prognosis is controversial. This review aimed to quantitatively examine the latest evidence on this question.DesignAn updated systematic review and meta-analysis on the association between LKB1 expression and prognosis of patients with solid tumours were performed.Data sourcesEligible studies were identified through literature searches from database establishment until 15 June 2018 in the following databases: Embase, PubMed, Web of Science, Cochrane Library, China National Knowledge Infrastructure and Wan Fang databases.Eligibility criteriaThe association between LKB1 expression and clinicopathological characteristics, overall survival (OS), disease-free survival (DFS) and relapse-free survival (RFS) of patients with solid tumours were reported. Sufficient data were available to calculate the OR or HR and 95% CI.Data extraction and synthesisRelevant data were meta-analysed for OS, DFS, RFS and various clinical parameters.ResultsThe systematic review included 25 studies containing 6012 patients with solid tumours. Compared with patients with high LKB1 expression, patients with low expression showed significantly shorter OS in univariate analysis (HR=1.63, 95% CI 1.35 to 1.97, p<0.01) and multivariate analysis (HR=1.61, 95% CI 1.26 to 2.06, p<0.01). In contrast, the two groups showed similar DFS in univariate analysis (HR=1.49, 95% CI 0.73 to 3.01, p=0.27) as well as similar RFS in univariate analysis (HR=1.44, 95% CI 0.65 to 3.17, p=0.37) and multivariate analysis (HR=1.02, 95% CI 0.42 to 2.47, p=0.97). Patients with low LKB1 expression showed significantly worse tumour differentiation (OR=1.71, 95% CI 1.14 to 2.55, p<0.01), larger tumours (OR=1.68, 95% CI 1.24 to 2.27, p<0.01), earlier lymph node metastasis (OR=1.43, 95% CI 1.26 to 1.62, p<0.01) and more advanced tumour, node, metastases (TNM) stage (OR=1.80, 95% CI 1.56 to 2.07, p<0.01).ConclusionLow LKB1 expression predicts shorter OS, worse tumour differentiation, larger tumours, earlier lymph node metastasis and more advanced TNM stage. Low LKB1 expression may be a useful biomarker of poor clinicopathology and prognosis.

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Impact of c-erbB-2 Protein on 5-year Survival Rate of Gastric Cancer Patients after Surgery: A Cohort Study and Meta-analysis

Tumori Journal ◽

10.5301/tj.5000444 ◽

2015 ◽

Vol 103 (3) ◽

pp. 249-254 ◽

Cited By ~ 4

Author(s):

Hao Wu ◽

Zhenzhai Cai ◽

Guangrong Lu ◽

Shuguang Cao ◽

He Huang ◽

...

Keyword(s):

Gastric Cancer ◽

Lymph Node ◽

Survival Rate ◽

Lymph Node Metastasis ◽

Protein Expression ◽

Meta Analysis ◽

Clinicopathological Characteristics ◽

Node Metastasis ◽

Positive Expression ◽

Significant Difference

Objective To explore the association of c-erbB-2 protein expression with clinicopathological characteristics and prognosis of gastric cancer (GC) after surgery. Methods A total of 133 patients undergoing surgical resection for GC between March 2006 and January 2009 in the Second Affiliated Hospital of Wenzhou Medical University were included in this study. c-erbB-2 protein expression was determined by immunohistochemistry. Afterwards, a meta-analysis was performed to further confirm the association between c-erbB-2 protein expression and GC by employing stringent inclusion and exclusion criteria. All data analyses were conducted with STATA 12.0 and SPSS 19.0. Results There was no significant difference in c-erbB-2 expression among patients with various parameters including age, gender and histological types (all p>0.05). Among 133 GC patients, 32 patients presented c-erbB-2-positive expression and 101 presented c-erbB-2-negative expression (24.1% vs. 75.9%). The c-erbB-2-positive expression rate was significantly higher in GC tissues of patients with lymph node metastasis than those without. Similarly, a significant increase in c-erbB-2 expression was observed in well/moderately differentiated GC tissues compared with poorly differentiated GC. Patients with negative c-erbB-2 expression had a higher 5-year survival rate than those with positive c-erbB-2 expression, which was consistent with the results of the meta-analysis (OR = 0.54, 95% CI 0.37-0.80, p = 0.002). Conclusions Our study demonstrated that high expression of c-erbB-2 protein was strongly associated with lymph node metastasis, histological differentiation and 5-year survival rate in GC patients after surgery.

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LncRNA AWPPH as a Prognostic Predictor in Human Cancers: Evidence From Meta-analysis

10.21203/rs.3.rs-121126/v1 ◽

2020 ◽

Author(s):

Yongfeng Li ◽

Xinmiao Rui ◽

Daobao Chen ◽

Haojun Xuan ◽

Hongjian Yang ◽

...

Keyword(s):

Overall Survival ◽

Lymph Node ◽

Lymph Node Metastasis ◽

Tumor Size ◽

Vascular Invasion ◽

Meta Analysis ◽

Clinicopathological Features ◽

Tnm Stage ◽

Node Metastasis ◽

Human Cancers

Abstract Background: Long noncoding RNA associated with poor prognosis of hepatocellular carcinoma (AWPPH) is a novel oncogene and dysregulated in a variety of human cancers. It has been revealed to be associated with the clinicopathological features and prognosis. However, the prognostic value of AWPPH in various cancers remains unclear. Therefore, we perform this meta-analysis to evaluate the relationship between AWPPH expression and clinical outcomes in human cancers.Methods: Comprehensive literature search was performed in PubMed, Web of Science, CNKI and Wangfang databases, and eligible studies were obtained according to the inclusion and exclusion criteria. The pooled hazard ratios (HRs) and odds ratios (ORs) were applied to assess the clinical value of AWPPH expression for overall survival (OS) and clinicopathological features.Results: A total of 19 articles including 1699 cancer patients were included in the study. The pooled results demonstrated that evaluated AWPPH expression was positively related to a poorer overall survival of patients with cancers (HR=1.79, 95%CI: 1.44-2.14, P<0.001). Subgroup analysis revealed that tumor type and sample size affect the predictive value of AWPPH on OS, whereas cut-off value and HR estimation method have no impact on it. In addition, the pooled data also showed that AWPPH was positively linked to advanced TNM stage (OR=2.67, 95%CI: 1.86-3.83, P<0.001) , bigger tumor size (OR=2.64, 95%CI:1.47-4.73, P=0.001), macro-vascular invasion (OR=2.08, 95%CI: 1.04-4.16, P=0.04) and lymph node metastasis (OR=2.68, 95%CI: 1.82-3.96, P<0.001). Moreover, the results of the trim and fill analysis confirmed the reliability of our finding. Conclusions: Upregulation of AWPPH was associated with advanced TNM stage, bigger tumor size, worse lymph node metastasis, macro-vascular invasion, and shorter overall survival, suggesting that AWPPH may serve as a biomarker for prognosis and clinicopathological characteristics in human cancers.

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Prognostic value of low microRNA-34a expression in human gastrointestinal cancer: a systematic review and meta-analysis

BMC Cancer ◽

10.1186/s12885-020-07751-y ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Yan-Ling Chen ◽

Xiao-Lin Liu ◽

Ling Li

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Meta Analysis ◽

Disease Free Survival ◽

Tnm Stage ◽

Cancer Prognosis ◽

Expression Level ◽

Free Survival ◽

Node Metastasis

Abstract Background Mounting evidence shows that microRNA-34a (miR-34a) is involved in cancer prognosis. Therefore, we summarize the predictive role of miR-34a for survival in patients with gastrointestinal cancers (GICs). Methods All eligible studies were found by searching PubMed, Web of Science and EMBASE, and survival results were extracted. Then, the hazard ratio (HR) with the corresponding 95% confidence interval (CI) was calculated to evaluate the prognostic role of miR-34a in GICs. The association between miR-34a expression and clinicopathological characteristics was estimated by odds ratios (ORs) and 95% CIs. Results A total of 20 studies were included in this meta-analysis. For overall survival (OS), lower miR-34a expression could probably predict poorer outcome in GICs, with a pooled HR of 1.86 (95% CI: 1.52–2.28, P < 0.01). For disease-free survival (DFS), progression-free survival (PFS), and recurrence-free survival (RFS), lower miR-34a expression was related to worse DFS/PFS/RFS with a pooled HR of 1.86 (95% CI: 1.31–2.63, P < 0.01). A significant relation of differentiation/TNM stage/lymphatic metastasis and the expression level of miR-34a was identified. Conclusion This meta-analysis revealed that lower miR-34a expression is significantly connected with worse OS and DFS/PFS/RFS in GIC patients. In addition, the miR-34a expression level is relatively lower in patients with lymph node metastasis than in patients without lymph node metastasis, and decreased miR-34a expression levels are linked to poor tumour differentiation and late TNM stage. MiR-34a may become a new factor for the prognosis prediction and progression of GICs.

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Tumour-Infiltrating Lymphocytes (TILs) and PD-L1 Expression Correlate with Lymph Node Metastasis, High-Grade Transformation and Shorter Metastasis-Free Survival in Patients with Acinic Cell Carcinoma (AciCC) of the Salivary Glands

Cancers ◽

10.3390/cancers13050965 ◽

2021 ◽

Vol 13 (5) ◽

pp. 965

Author(s):

Selina Hiss ◽

Markus Eckstein ◽

Patricia Segschneider ◽

Konstantinos Mantsopoulos ◽

Heinrich Iro ◽

...

Keyword(s):

Lymph Node ◽

Lymph Node Metastasis ◽

Lymph Node Metastases ◽

Immune Cell ◽

High Grade ◽

Free Survival ◽

Node Metastasis ◽

Node Metastases ◽

High Grade Transformation ◽

Infiltrating Lymphocytes

Objectives: The aim of this study was to assess the number of tumour-infiltrating lymphocytes (TILs) and the expression of Programmed Cell Death 1 Ligand 1 (PD-L1) in Acinic Cell Carcinoma (AciCC) of the salivary glands, to enable a correlation with clinico-pathological features and to analyse their prognostic impact. Methods: This single centre retrospective study represents a cohort of 36 primary AciCCs with long-term clinical follow-up. Immunohistochemically defined immune cell subtypes, i.e., those expressing T-cell markers (CD3, CD4 and CD8) or a B-cell marker (CD20) were characterized on tumour tissue sections. The number of TILs was quantitatively evaluated using software for digital bioimage analysis (QuPath). PD-L1 expression on the tumour cells and on immune cells was assessed immunohistochemically employing established scoring criteria: tumour proportion score (TPS), Ventana immune cell score (IC-Score) and combined positive score (CPS). Results: Higher numbers of tumour-infiltrating T- and B- lymphocytes were significantly associated with high-grade transformation. Furthermore, higher counts of T-lymphocytes correlated with node-positive disease. There was a significant correlation between higher levels of PD-L1 expression and lymph node metastases as well as the occurrence of high-grade transformation. Moreover, PD-L1 CPS was associated with poor prognosis regarding metastasis-free survival (p = 0.049). Conclusions: The current study is the first to demonstrate an association between PD-L1 expression and lymph node metastases as well as grading in AciCCs. In conclusion, increased immune cell infiltration of T and B cells as well as higher levels of PD-L1 expression in AciCC in association with high-grade transformation, lymph node metastasis and unfavourable prognosis suggests a relevant interaction between tumour cells and immune cell infiltrates in a subset of AciCCs, and might represent a rationale for immune checkpoint inhibition.

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