Tumor microenvironment and epithelial-mesenchymal transition in bladder cancer: Cytokines in the game?

Cláudia Martins-Lima; Ugo Chianese; Rosaria Benedetti; Lucia Altucci; Carmen Jerónimo; Margareta P Correia

doi:10.3389/fmolb.2022.1070383

Tumor microenvironment and epithelial-mesenchymal transition in bladder cancer: Cytokines in the game?

Front Mol Biosci. 2023 Jan 9:9:1070383. doi: 10.3389/fmolb.2022.1070383. eCollection 2022.

Authors

Cláudia Martins-Lima^{1

2}, Ugo Chianese², Rosaria Benedetti², Lucia Altucci^{2

3

4}, Carmen Jerónimo^{1

5}, Margareta P Correia^{1

5}

Affiliations

¹ Cancer Biology and Epigenetics Group, Research Center of IPO Porto (CI-IPOP)/RISE@CI-IPOP (Health Research Network), Portuguese Oncology Institute of Porto (IPO Porto) and Porto Comprehensive Cancer Center (Porto.CCC) Raquel Seruca, Porto, Portugal.
² Department of Precision Medicine, University of Campania "Luigi Vanvitelli", Naples, Italy.
³ BIOGEM, Molecular Biology and Genetics Research Institute, Avellino, Italy.
⁴ IEOS, Institute of Endocrinology and Oncology, Naples, Italy.
⁵ Department of Pathology and Molecular Immunology at School of Medicine and Biomedical Sciences, University of Porto (ICBAS-UP), Porto, Portugal.

Abstract

Bladder cancer (BlCa) is a highly immunogenic cancer. Bacillus Calmette-Guérin (BCG) is the standard treatment for non-muscle invasive bladder cancer (NMIBC) patients and, recently, second-line immunotherapies have arisen to treat metastatic BlCa patients. Understanding the interactions between tumor cells, immune cells and soluble factors in bladder tumor microenvironment (TME) is crucial. Cytokines and chemokines released in the TME have a dual role, since they can exhibit both a pro-inflammatory and anti-inflammatory potential, driving infiltration and inflammation, and also promoting evasion of immune system and pro-tumoral effects. In BlCa disease, 70-80% are non-muscle invasive bladder cancer, while 20-30% are muscle-invasive bladder cancer (MIBC) at the time of diagnosis. However, during the follow up, about half of treated NMIBC patients recur once or more, with 5-25% progressing to muscle-invasive bladder cancer, which represents a significant concern to the clinic. Epithelial-mesenchymal transition (EMT) is one biological process associated with tumor progression. Specific cytokines present in bladder TME have been related with signaling pathways activation and EMT-related molecules regulation. In this review, we summarized the immune landscape in BlCa TME, along with the most relevant cytokines and their putative role in driving EMT processes, tumor progression, invasion, migration and metastasis formation.

Keywords: bladder cancer; cytokines/chemokines; epithelial-mesenchymal transition (EMT); immune cells; tumor microenvironment (TME).

Publication types

Review

Grants and funding

This study was funded by the Research Center of Portuguese Institute of Porto (CI-IPOP-FBGEBC-27 and CI-IPOP-PI 137), and also by Associazione Italiana per la Ricerca sul Cancro (AIRC IG17217 to LA); the Italian Ministry for University and Research (PRIN 2015- 20152TE5PK, to LA); the project “Epigenetic Hallmarks of Multiple Sclerosis” (acronym Epi-MS) (id:415, Merit Ranking Area ERC LS) in VALERE 2019 Program (to RB); Blueprint 282510 (to LA); Campania Regional Government Technology Platform Lotta alle Patologie Oncologiche: iCURE (to LA); Campania Regional Government FASE2: IDEAL (to LA); MIUR, Proof of Concept POC01_00043 (to LA); Programma V:ALERE 2020 - Progetto competitivo “CIRCE” in risposta al bando D.R. n. 138 del 17/02/2020 (to RB). CM-L is fellow from a grant of UniCampania, Naples, IT (2020-UNA2CLE-0203198) enrolled in the PhD program in Translational Medicine, Department of Precision Medicine, University of Campania “Luigi Vanvitelli”, Italy. MPC is funded by FCT (CEECINST/00091/2018).