Reconnaissance of tumor immune microenvironment spatial heterogeneity in metastatic renal cell carcinoma and correlation with immunotherapy response

• DOI: 10.1111/cei.13567
• Publication Date: 2020-12-21T23:58:52Z
• Authors: A Hajiran; N Chakiryan; A M Aydin; L Zemp; J Nguyen; J M Laborde; J Chahoud; P E Spiess; S Zaman; S Falasiri; M Fournier; J K Teer; J Dhillon; S McCarthy; C Moran-Segura; E N Katende; W J Sexton; J M Koomen; J Mulé; Y Kim; B Manley
• Keywords: Adult; Male; 0301 basic medicine; 0303 health sciences; Macrophages; Kaplan-Meier Estimate; Middle Aged; Kidney Neoplasms; 3. Good health; 03 medical and health sciences; Lymphocytes, Tumor-Infiltrating; Treatment Outcome; T-Lymphocyte Subsets; Immune System; Biomarkers, Tumor; Tumor Microenvironment; Humans; Female; Immunotherapy; Carcinoma, Renal Cell; Aged

A clearer understanding of the tumor immune microenvironment (TIME) in metastatic clear cell renal carcinoma (ccRCC) may help to inform precision treatment strategies. We sought identify clinically meaningful TIME signatures ccRCC. studied tumors from 39 patients with ccRCC using quantitative multiplexed immunofluorescence and relevant marker panels. Cell densities were analyzed three regions interest (ROIs): core, tumor-stroma interface stroma. Patients stratified into low- high-marker density groups median values as thresholds. Log-rank Cox regression analyses while controlling for clinical variables used compare survival outcomes patterns distributions. There significant associations increased macrophage (CD68+ CD163+ CD206+ ) poor across multiple ROIs primary tumors. In tumors, T-bet+ T helper type 1 (Th1) was highest at tumor-stromal (P = 0·0021), co-expression CD3 T-bet associated improved overall 0·015) after immunotherapy 0·014). samples, decreased forkhead box protein 3 (FoxP3)+ regulatory correlated 0·016). Increased markers Th1 within outcomes. Immune such FoxP3 showed consistent levels TIME, whereas others, T-bet, demonstrated variance distinct ROIs. These findings suggest that profiling outside core