AUTHOR=Wang Yongfeng , Yin Ci , Geng Lele , Cai Weiyang 

TITLE=Immune Infiltration Landscape in Clear Cell Renal Cell Carcinoma Implications

JOURNAL=Frontiers in Oncology

VOLUME=Volume 10 - 2020

YEAR=2021

URL=https://www.frontiersin.org/journals/oncology/articles/10.3389/fonc.2020.491621

DOI=10.3389/fonc.2020.491621

ISSN=2234-943X

ABSTRACT=Background: The malignant phenotypes of cancer are defined not only by its intrinsic tumor cells but also by the tumor infiltrating immune cells (TIICs). Renal cell carcinoma (RCC) immune microenvironment plays an important role in tumorigenesis. This research investigated the characteristics of immune cell invasion of renal cell carcinoma and provided clues for future clinical implementation. 
Methods: Retrospectively, RCC gene expression was analyzed with appropriate clinicopathological data from the Cancer Genome Atlas (TCGA) and GEO database up to June 2019. The CIBERSORT algorithm, meta-analysis, principal component analysis (PCA), Single-Sample Gene Set Enrichment Analysis (ssGSEA) and hierarchical agglomerative clustering were used to measure and evaluate the respective proportions of 22 cell types of immune infiltration using normalized gene expression data.
Results: The distribution of tumour infiltrating immune cells composition of RCC tissue was entirely different from normal. Naive B cells (95 % CI, − 0.8 to -0.09; P< 0.01), plasma cells (95 % CI, −0.84 to -0.17; P< 0.01), monocytes (95 % CI, − 0.56 to 0.05; P< 0.01), resting dendritic cells (95 % CI, − 0.80 to -0.38; P = 0.05) and resting mast cells (95 % CI, − 0.44 to -0.11; P = 0.24) exhibited a decrease tendency; whereas CD8 T cells (95 % CI, 0.14 to 0.71; P< 0.01), resting memory CD4 T cells (95 % CI, 0.26 to 1.09; P< 0.01), M0 macrophages (95 % CI, 0.12 to 0.64; P< 0.01) and M1 macrophages  (95 % CI, 0.60 to 1.13; P< 0.01) exhibited a increasing tendency in RCC tissues. We also focused on evaluating the association with TIICs subpopulations and clinical features and molecular subtypes. TIICs subpopulation, especially Macrophages subgroup, T follicular helper (Tfh) cells and CD8 T cells, all contribute to tumorigenesis. Unsupervised clustering analysis revealed that there existed two distinct TIICs subgroups with different survival patterns. 
Conclusions: TIICs are extensively involved in the pathogenesis and development of the RCC. Characterizing the composition of TIICs influences the metabolism of tumors, activity, level, stage, and survival of patients. Collectively, the TIIC analysis has the potential to assist in the assessment and selection of RCC prognosis and treatment.