Dataset Information

TIGIT and PD-1 expression atlas predicts response to adjuvant chemotherapy and PD-L1 blockade in muscle-invasive bladder cancer.

ABSTRACT:

Background

TIGIT and PD-1 are checkpoint receptors that could regulate the functional status of immune cells through independent pathways. However, the clinical significance of immune classification based on TIGIT and PD-1 expression remains unclear in muscle-invasive bladder cancer (MIBC).

Methods

Patients with MIBC from four independent cohorts were categorised into three clusters. Survival analysis conducted through Kaplan-Meier curves and Cox regression model. Immune contexture was measured by immunohistochemistry and CIBERSORT algorithm. Twenty-five fresh tumour tissue samples were utilised to evaluate functional state of CD8⁺ T cells by flow cytometry.

Results

Cluster I (TIGIT^lowPD-1^low) contained widely poor immune infiltrates with higher FGFR3 mutation, Cluster II (TIGIT^lowPD-1^high) exhibited a highly infiltrated contexture with increased cytolytic CD8⁺ T cells and had the best prognosis, Cluster III (TIGIT^high) presented a suppressive tumour microenvironment (TME) featured by exhausted CD8⁺ T cells and basal molecular subtype. Patients of Cluster III had the worst survival but could benefit more from adjuvant chemotherapy and anti-PD-L1 immunotherapy, and also presented limited FGFR3 signalling signature but activated immunotherapeutic and EGFR-associated pathway.

Conclusions

TIGIT/PD-1-based risk stratification with distinct immune and molecular features could be served as a predictor for systematic therapeutic response including adjuvant chemotherapy and immunotherapy in MIBC patients.

SUBMITTER: Liu Z

PROVIDER: S-EPMC9042924 | biostudies-literature | 2022 May

REPOSITORIES: biostudies-literature

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Publications

TIGIT and PD-1 expression atlas predicts response to adjuvant chemotherapy and PD-L1 blockade in muscle-invasive bladder cancer.

Liu Zhaopei Z Zeng Han H Jin Kaifeng K Yu Yanze Y You Runze R Zhang Hongyi H Liu Chunnan C Su Xiaohe X Yan Sen S Chang Yuan Y Liu Li L Xu Le L Xu Jiejie J Zhu Yu Y Wang Zewei Z

British journal of cancer 20220117 9

<h4>Background</h4>TIGIT and PD-1 are checkpoint receptors that could regulate the functional status of immune cells through independent pathways. However, the clinical significance of immune classification based on TIGIT and PD-1 expression remains unclear in muscle-invasive bladder cancer (MIBC).<h4>Methods</h4>Patients with MIBC from four independent cohorts were categorised into three clusters. Survival analysis conducted through Kaplan-Meier curves and Cox regression model. Immune contextur ...[more]

PMID: 35039625

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Project description:BackgroundThe expression alterations of B4GALT1 have been noted in some types of cancer and they are related to cancer cell proliferation, invasiveness, metastasis, and drug resistance. We aimed to establish the expression of B4GALT1 in bladder cancer and its connection to patient outcomes, as well as forecasting the advantages of adjuvant chemotherapy (ACT) in patients with muscle-invasive bladder cancer (MIBC).MethodsThere were 142 and 112 MIBC patients who were consecutively recruited and treated via radical cystectomy from 2008 to 2012 in Shanghai Zhongshan Hospital and Fudan University Shanghai Cancer Center (FUSCC), respectively. Tissue microarrays (TMAs) were constructed in triplicate from specimens that had been fixed in formalin and embedded in paraffin samples. Immunohistochemistry was conducted to evaluate B4GALT1 expression in tumor cores, the connection between B4GALT1 expression and patients' clinical characteristics, and clinical results.ResultsB4GALT1 expression was not connected to clinical prognosis markers, but it was linked to overall survival (OS) (P = 0.013 and P = 0.010, respectively) in the two groups. Moreover, the high levels of B4GALT1 expression were independent indicators of poor OS (P = 0.026 and P = 0.046, respectively). Inclusion of B4GALT1 in the prognostic model revealed a greater predictive accuracy than the primary models. In addition, no differences were observed between B4GALT1 expression (low vs. high) and CD8+ T cell infiltration density (number/cm2) within tumor cores, but there was a positive Pearson correlation between B4GALT1 expression and expression of inhibitory receptor ligands, such as PD-L1 and CTLA4. Most significantly, the advantage of ACT noted in pT3/4 or N+ bladder cancer patients with low B4GALT1 expression was greater than in patients with a high B4GALT1 expression.ConclusionsOur evaluation indicated that B4GALT1 may be a possible prognosticator of MIBC, and it may be a predictive marker for the choice of ACT in pT3/4 or N+ patients.

Project description:Introduction and objectivesPD-L1 and B7-H3 have been found to be overexpressed in urothelial carcinoma (UC) of the urinary bladder. Recent studies have also demonstrated that B7-H3 and PD-L1 can promote resistance to platinum-based drugs but the predictive value of B7-H3 expression in patients treated with platinum-based chemotherapy is unknown. This study aims to investigate the association of PD-L1 and B7-H3 tumor expression with oncological outcomes in patients who underwent radical cystectomy (RC) and received subsequent adjuvant chemotherapy.Materials and methodsImmunohistochemistry was performed on paraffin-embedded sections from bladder and lymph node specimens of 81 patients who had RC for bladder cancer. PD-L1 and B7-H3 expression on tumor cells was assessed by immunohistochemistry in both primary tumors and lymph node specimens. Association with clinicopathologic outcomes was determined using Fisher's exact test and postoperative survival using Kaplan-Meier survival curves and Cox regression model.ResultsB7-H3 expression in cystectomy specimens was more common than PD-L1 expression (72.8% vs. 35.8%). For both markers, no association was found with pathologic tumor stage, lymph node (LN) status, and histological subtype. Similar findings were observed for double-positive tumors (PD-L1+B7-H3+). Concordance between the primary tumor and patient-matched lymph nodes was found in 76.2% and 54.1% of patients for PD-L1 and B7-H3, respectively. PD-L1 tumor expression was not associated with oncologic outcomes. However, B7-H3 expression was associated with recurrence-free survival (HR: 2.38, 95% CI 1.06-5.31, p = 0.035) and cancer-specific survival (HR: 2.67, 95% CI 1.18-6.04, p = 0.019).ConclusionsIn our single institutional study, B7-H3 is highly expressed in patients with UC treated with adjuvant chemotherapy and it was associated with decreased recurrence-free survival and cancer-specific survival. Pending further validation in larger cohorts, B7-H3 expression may function as a predictor of response to adjuvant chemotherapy and thus be useful in patient and regimen selection.

Dataset Information

TIGIT and PD-1 expression atlas predicts response to adjuvant chemotherapy and PD-L1 blockade in muscle-invasive bladder cancer.

Background

Methods

Results

Conclusions

Publications

TIGIT and PD-1 expression atlas predicts response to adjuvant chemotherapy and PD-L1 blockade in muscle-invasive bladder cancer.

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