Cellular and Molecular Players in the Tumor Microenvironment of Renal Cell Carcinoma.

Globally, clear-cell renal cell carcinoma (ccRCC) represents the most prevalent type of kidney cancer. Surgery plays a key role in the treatment of this cancer, although one third of patients are diagnosed with metastatic ccRCC and about 25% of patients will develop a recurrence after nephrectomy with curative intent. Molecular-target-based agents, such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), are recommended for advanced cancers. In addition to cancer cells, the tumor microenvironment (TME) includes non-malignant cell types embedded in an altered extracellular matrix (ECM). The evidence confirms that interactions among cancer cells and TME elements exist and are thought to play crucial roles in the development of cancer, making them promising therapeutic targets. In the TME, an unfavorable pH, waste product accumulation, and competition for nutrients between cancer and immune cells may be regarded as further possible mechanisms of immune escape. To enhance immunotherapies and reduce resistance, it is crucial first to understand how the immune cells work and interact with cancer and other cancer-associated cells in such a complex tumor microenvironment.

Journal of clinical medicine. 2023 Jun 07*** epublish ***

Francesco Lasorsa, Monica Rutigliano, Martina Milella, Matteo Ferro, Savio Domenico Pandolfo, Felice Crocetto, Octavian Sabin Tataru, Riccardo Autorino, Michele Battaglia, Pasquale Ditonno, Giuseppe Lucarelli

Urology, Andrology and Kidney Transplantation Unit, Department of Precision and Regenerative Medicine and Ionian Area, University of Bari "Aldo Moro", 70124 Bari, Italy., Division of Urology, European Institute of Oncology, IRCCS, 71013 Milan, Italy., Department of Neurosciences and Reproductive Sciences and Odontostomatology, University of Naples "Federico II", 80131 Naples, Italy., Department of Simulation Applied in Medicine, George Emil Palade University of Medicine, Pharmacy, Sciences and Technology, 540139 Târgu Mureș, Romania., Department of Urology, Rush University Medical Center, Chicago, IL 60612, USA.