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Latency-associated peptide identifies therapeutically resistant muscle-invasive bladder cancer with poor prognosis
- Source :
- Cancer Immunology, Immunotherapy. 71:301-310
- Publication Year :
- 2021
- Publisher :
- Springer Science and Business Media LLC, 2021.
-
Abstract
- Latency-associated peptide (LAP) was identified as crucial immune regulator in tumor microenvironment (TME) in recent researches. In this study, we aimed to estimate the predictive value of LAP expression for clinical survival and therapeutic response in muscle-invasive bladder cancer (MIBC). Our study encompassed 140 MIBC patients from Zhongshan Hospital (ZSHS cohort), 401 patients from The Cancer Genome Atlas (TCGA cohort) and 195 patients received PDL1 blockade from IMvigor210 trial. Survival analyses were conducted through Kaplan–Meier curve and Cox regression model. LAP expression and its association with immune contexture were evaluated in ZSHS and TCGA cohort. We found that high intratumoral LAP+ cells infiltration anticipated inferior survival and adjuvant chemotherapy (ACT) response, and was closely related to an immunoevasive contexture with increased M2 macrophages, neutrophils and conspicuously a cluster of highly exhausted CD8+ T cells. The combinational analysis of LAP+ cells and CD8+ T cells infiltration stratified patients into distinct risk groups with implications for therapeutic sensitivity to PDL1 blockade and refinement of molecular classification in MIBC. LAP expression was correlated with patients’ inferior prognosis, ACT-tolerance and an immunoevasive TME with exhausted CD8+ T cell infiltration, suggesting that LAP could serve as a promising therapeutic target in MIBC. Simultaneously, our novel TME classification based on LAP+ cells and CD8+ T cells infiltration and its potential in appraising PDL1 blockade application for MIBC patients deserved further validation.
- Subjects :
- Oncology
Cancer Research
medicine.medical_specialty
Immunology
CD8-Positive T-Lymphocytes
03 medical and health sciences
0302 clinical medicine
Immune system
Transforming Growth Factor beta
Internal medicine
Tumor Microenvironment
Humans
Immunology and Allergy
Medicine
Protein Precursors
Immune Checkpoint Inhibitors
Retrospective Studies
Muscle Neoplasms
Tumor microenvironment
Bladder cancer
business.industry
Proportional hazards model
digestive, oral, and skin physiology
Prognosis
medicine.disease
Blockade
Survival Rate
Urinary Bladder Neoplasms
Chemotherapy, Adjuvant
Drug Resistance, Neoplasm
Cohort
Tumor Escape
Peptides
business
human activities
Infiltration (medical)
CD8
Follow-Up Studies
030215 immunology
Subjects
Details
- ISSN :
- 14320851 and 03407004
- Volume :
- 71
- Database :
- OpenAIRE
- Journal :
- Cancer Immunology, Immunotherapy
- Accession number :
- edsair.doi.dedup.....6de342beed09dbf39b772cd583257de1