Immune infiltration in renal cell carcinoma

Area of Science:

• Oncology
• Immunology
• Genomics

Background:

• Immune cell infiltration in tumors significantly influences clinical outcomes in renal cell carcinoma (RCC).
• Tumor-infiltrating immune cells (TIICs) play a crucial role in cancer progression and represent potential therapeutic targets.
• Understanding the composition and prognostic significance of TIICs is vital for advancing RCC treatment strategies.

Purpose of the Study:

• To comprehensively analyze the composition of TIICs in RCC.
• To determine the independent prognostic value of various TIICs in different RCC subtypes.
• To identify potential biomarkers and therapeutic targets for RCC immunotherapy.

Main Methods:

• Utilized the CIBERSORT algorithm to quantify proportions of 22 immune cell types from gene expression profiles of 891 RCC tumors.
• Employed Cox regression analysis to assess the association between TIIC proportions and immune checkpoint modulators with overall survival (OS).
• Stratified analysis was performed across different RCC subtypes: chromophobe carcinoma (KICH), renal clear cell carcinoma (KIRC), and renal papillary cell carcinoma (KIRP).

Main Results:

• CD8+ T cells correlated with prolonged OS in KICH (HR=0.09, P=0.03).
• Increased regulatory T cells were linked to worse outcomes in KIRC (HR=1.59, P<0.01).
• M1 macrophages indicated favorable prognosis, while M2 macrophages predicted worse outcomes in KIRP (HR=0.43, P<0.01 and HR=2.55, P<0.01, respectively).
• Immune checkpoint molecules CTLA4 and LAG3 were associated with poor prognosis in KIRC, while IDO1 and PD-L2 showed similar associations in KIRP.

Conclusions:

• TIICs are significant determinants of prognosis across various subtypes of RCC.
• Specific immune cell populations and their proportions offer prognostic insights.
• Findings highlight potential immune-related biomarkers and therapeutic targets for personalized immunotherapy in RCC.