Histologic-Based Tumor-Associated Immune Cells Status in Clear Cell Renal Cell Carcinoma Correlates with Gene Signatures Related to Cancer Immunity and Clinical Outcomes

Abstract

The three-tier immunophenotype (desert, excluded, and inflamed) and the four-tier immunophenotype (cold, immunosuppressed, excluded, and hot) have been linked to prognosis and immunotherapy response. This study aims to evaluate whether immunophenotypes of clear cell renal cell carcinoma, identified on hematoxylin and eosin-stained slides, correlate with gene expression signatures related to cancer immunity, and clinical outcomes. We evaluated tumor-associated immune cells (TAICs) status using three methodologies: three-tier immunophenotype based on the location of TAICs, four-tier immunophenotype considering both the location and degree of TAICs and inflammation score focusing only on the degree of TAICs, using a localized clear cell renal cell carcinoma cohort (n = 436) and The Cancer Genome Atlas (TCGA)-KIRC cohort (n = 162). We evaluated the association of the TAICs status assessed by three methodologies with CD8 and PD-L1 immunohistochemistry and immune gene expression signatures by TCGA RNA-sequencing data. All three methodologies correlated with immunohistochemical and immune gene expression signatures. The inflammation score and the four-tier immunophenotype showed similarly higher accuracy in predicting recurrence-free survival and overall survival compared to the three-tier immunophenotype. In conclusion, a simple histologic assessment of TIACs may predict clinical outcomes and immunotherapy responses.

Defining Melanoma Immune Biomarkers—Desert, Excluded, and Inflamed Subtypes—Using a Gene Expression Classifier Reflecting Intratumoral Immune Response and Stromal Patterns

“…In this setting, our findings combining transcriptome and histology data, although with their own limitations, carry an element of novelty and contribute to the understanding of the tissue-specific immune contexture in melanoma. Our definition of desert, excluded, and inflamed immune subtypes is aligned with related reports on other cancer types, such as ovarian [14,51,52], lung [53][54][55], head and neck, [52,56,57] breast [55,58], bladder [52,53], gastric [52], colorectal [52], hepatocellular [59], pancreatic [60], and renal cancer [61], and contributes to developing agreement on universal immune contexture elements among different cancer localizations.…”

Exploration and validation of a combined immune and metabolism gene signature for prognosis prediction of colorectal cancer

“…As an essential component of immunotherapy, analysis of the tumor immune microenvironment (TIME) contributes to prediction of responsiveness to immunotherapy. Promising clinical results have been achieved in a variety of cancers by reprogramming the immunosuppressed state in tumors to an immune activated state ( 24 ). In our study, we explored the relationship between riskScore and immune cells in TIME and found that the high-risk group displayed a more abundant macrophage infiltration.…”

Identification of Immune and Hypoxia Risk Classifier to Estimate Immune Microenvironment and Prognosis in Cervical Cancer

“…Accumulating evidence has identi ed the immunotherapy as a promising intervention for cancer patients [11]. By reprograming the immunosuppressive state in the "cold tumor" into an activated one, the usage of immune checkpoint inhibitors as well as some cell-speci c compounds has achieved exciting clinic outcome in multiple cancers [12,13]. However, immunotherapy in CC remain largely unexplored.…”