Immune infiltration in renal cell carcinoma

• Published in: Cancer science Vol. 110; no. 5; pp. 1564 - 1572
• Main Authors: Zhang, Shichao, Zhang, Erdong, Long, Jinhua, Hu, Zuquan, Peng, Jian, Liu, Lina, Tang, Fuzhou, Li, Long, Ouyang, Yan, Zeng, Zhu
• Format: Journal Article
• Language: English
• Published: England John Wiley & Sons, Inc 01.05.2019; John Wiley and Sons Inc
• Subjects: Algorithms; Antigens, CD - metabolism; Biomarkers; Carcinoma, Papillary - immunology; Carcinoma, Papillary - metabolism; Carcinoma, Papillary - pathology; Carcinoma, Renal Cell - immunology; Carcinoma, Renal Cell - metabolism; Carcinoma, Renal Cell - pathology; CD8 antigen; CD8-Positive T-Lymphocytes - metabolism; Clear cell-type renal cell carcinoma; Clinical outcomes; Colorectal cancer; CTLA-4 Antigen - metabolism; CTLA-4 protein; Female; Gene expression; genomic alterations; Humans; Immune checkpoint; Immunomodulation; Immunoregulation; Immunotherapy; Indoleamine-Pyrrole 2,3,-Dioxygenase - metabolism; Kidney cancer; Kidney Neoplasms - immunology; Kidney Neoplasms - metabolism; Kidney Neoplasms - pathology; Liver cancer; Lymphocytes; Lymphocytes T; Lymphocytes, Tumor-Infiltrating - metabolism; Macrophages; Macrophages - metabolism; Male; Medical prognosis; Metastases; Methods; Mutation; Neoplasm Staging; Original; overall survival; Patients; Prognosis; Programmed Cell Death 1 Ligand 2 Protein - metabolism; renal cell carcinoma; Studies; Survival Analysis; T-Lymphocytes, Regulatory - metabolism; Therapeutic applications; Tumors; tumor‐infiltrating immune cells; overall survival; tumor-infiltrating immune cells; renal cell carcinoma; genomic alterations; prognosis
• ISSN: 1347-9032; 1349-7006; 1349-7006
• DOI: 10.1111/cas.13996

Immune infiltration of tumors is closely associated with clinical outcome in renal cell carcinoma (RCC). Tumor‐infiltrating immune cells (TIICs) regulate cancer progression and are appealing therapeutic targets. The purpose of this study was to determine the composition of TIICs in RCC and further reveal the independent prognostic values of TIICs. CIBERSORT, an established algorithm, was applied to estimate the proportions of 22 immune cell types based on gene expression profiles of 891 tumors. Cox regression was used to evaluate the association of TIICs and immune checkpoint modulators with overall survival (OS). We found that CD8+ T cells were associated with prolonged OS (hazard ratio [HR] = 0.09, 95% confidence interval [CI].01‐.53; P = 0.03) in chromophobe carcinoma (KICH). A higher proportion of regulatory T cells was associated with a worse outcome (HR = 1.59, 95% CI 1.23‐.06; P < 0.01) in renal clear cell carcinoma (KIRC). In renal papillary cell carcinoma (KIRP), M1 macrophages were associated with a favorable outcome (HR = .43, 95% CI .25‐.72; P < 0.01), while M2 macrophages indicated a worse outcome (HR = 2.55, 95% CI 1.45‐4.47; P < 0.01). Moreover, the immunomodulator molecules CTLA4 and LAG3 were associated with a poor prognosis in KIRC, and IDO1 and PD‐L2 were associated with a poor prognosis in KIRP. This study indicates TIICs are important determinants of prognosis in RCC meanwhile reveals potential targets and biomarkers for immunotherapy development. We described the immune landscape in detail, revealing the distinct immune infiltration patterns of different subtypes and stages of RCC. We further revealed relationships between TIIC and molecular subtypes, tumor stages, recurrent genomic alterations and survival in RCC. Our work advances the understanding of immune response meanwhile reveals potential targets and biomarkers for immunotherapy development.