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

Abstract

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.

ZNF692 promotes the migration and response to immunotherapy of clear cell renal cell carcinoma cells by targeting metabolic pathway

“…Abundant infiltration of immune cells, particularly T cells, is one of the characteristics of the ccRCC tumor microenvironment [ 46 – 49 ]. Features of the tumor microenvironment heavily affect disease biology and may affect responses to systemic therapy especially immunotherapy [ 50 – 53 ]. In this context, immunotherapy for ccRCC has progressed considerably over the past decade, with new options ranging from cytokine treatments [ 54 ] to targeted therapies such as ICB and VEGF tyrosine kinase inhibitors (TKIs) [ 55 , 56 ].…”

Identification of a lactate metabolism-related lncRNAs signature for predicting the prognosis in patients with kidney renal clear cell carcinoma

“…KIRC characterized by a pronounced reliance on aerobic glycolysis, fundamentally presents as a metabolic disease distinguished by a reprogramming of energy metabolism ( 7 , 34 ). Enhanced glycolysis in tumor cells leads to elevated lactate levels, contributing to tumor microenvironment (TME) acidification.…”

“…Nevertheless, distant metastases that develop after surgery remain in a high proportion of patients ( 3 ). Despite therapeutic advances in immunotherapy and molecular targeted therapy ( 6 , 7 ), a significant proportion of patients do not respond to cancer treatment or even experience serious side effects ( 8 , 9 ). Consequently, it is imperative to explore potential prognostic markers for KIRC patients that may help to improve curative effect while reducing the burden of the disease.…”

Role of Exosomal Non-Coding RNA in the Tumour Microenvironment of Genitourinary System Tumours

“…87 Certain pathway components can be used as biomarkers for renal cell carcinoma. 88,89 Understanding the interactions between cells in the tumor microenvironment and cancer cells may provide new ideas for the prognostic and predictive characterization of RCC patients and for future drug development [90][91][92] .…”