CD103 and Intratumoral Immune Response in Breast Cancer

Abstract

Purpose: CD103 is expressed in several immune cell types but in the context of the intratumoral immune response may be most important as a marker of antigen-activated CD8 T cells.Methods: We have examined the prognostic significance of CD103 TILs in breast cancer by IHC in a cohort of 424 breast cancer patients.Results: CD103 TILs were present in all subtypes but were more abundant in ER-negative tumors where CD103 TILs were preferentially localized to the intraepithelial compartment. CD103 was associated with tumor size, tumor grade, and ER/PR status (P < 0.05). CD103 TIL density and the epithelial to stromal ratio was highest in the basal-like tumors. Intraepithelial CD103 but not intrastromal CD103 was associated with better relapse-free and overall survival in basal-like subtype tumors [HR ¼ 0.28; 95% confidence interval (CI), 0.17-0.72; P ¼ 0.0047 and HR ¼ 0.25; 95% CI, 0.17-0.66; P ¼ 0.0017, respectively). CD8 status showed similar but less significant associations, but the combination of dual CD103 þ CD8þ TIL status was the most strongly prognostic combination for relapse-free and overall survival (HR ¼ 0.10; 95% CI, 0.07-0.62; P ¼ 0.006 and HR ¼ 0.09; 95% CI, 0.07-0.57; P ¼ 0.003, respectively). Conclusions: CD103 TILs are indicative of a good prognosis specifically within the basal-like subtype of breast cancer. Clin Cancer Res; 22(24); 6290-7. Ó2016 AACR.

Assessing Tumor-infiltrating Lymphocytes in Solid Tumors: A Practical Review for Pathologists and Proposal for a Standardized Method From the International Immunooncology Biomarkers Working Group: Part 1: Assessing the Host Immune Response, TILs in Invasive Breast Carcinoma and Ductal Carcinoma In Situ, Metastatic Tumor Deposits and Areas for Further Research

“…For example, CD103 is a marker of a subset of CD8 + TILs that are most prevalent amongst intra-tumoral TILs and may reflect CD8 + T cells that have been engaged in an adaptive immune response [80]. Whereas TIL assessment on H&E was of borderline significance in a small cohort of basal-like invasive breast tumors, dual CD103 + CD8 + TIL status was strongly prognostic for relapse-free and overall survival [81]. The intensity and distribution of TILs in breast cancers is often heterogeneous [82,83] and it is recommended to give an overall assessment rather than focusing on hotspots of intense infiltration, based on a lack of data demonstrating any clinical significance of this heterogeneity [14].…”

Resident memory T cells, critical components in tumor immunology

“…Moreover, the expression of CD103 on TIL was associated with improved overall and recurrence-free survival in a retrospective cohort of urothelial cell carcinoma patients [29]. This integrin also appeared to be a biomarker of favorable prognosis in a large cohort of breast cancer patients [89]. However, the CD103 biomarker could also be expressed by CD4 + T cells and DC, which introduces bias in interpretation of results without double immunostaining with anti-CD8 mAb.…”

“…However, the CD103 biomarker could also be expressed by CD4 + T cells and DC, which introduces bias in interpretation of results without double immunostaining with anti-CD8 mAb. The epithelial location of CD103 + TIL is an even more significant prognosis marker compared to the stromal location, suggesting that intraepithelial CD8 + CD103 + cells encompass a higher proportion of tumor-specific T RM cells [27, 89]. This intratumoral infiltration of CD103 + TIL was associated with expression of E-cadherin on tumor cells in bladder cancer [29], but not in ovarian or breast cancer [26, 89].…”

Evaluation of Inflammatory Cells (Tumor Infiltrating Lymphocytes) in Solid Tumors

“…Nicméně fakt, že hodnocení intratumorózních lymfocytů v barvení HE (hematoxylin-eozin) může být v ně kte rých případech značně obtížné, mohl v důsledku vést k podhodnocení jejich významu. V současné době běží práce zabývající se potenciálním významem intratumorózních TIL a jejich detekcí s využitím imunohistochemie a/ nebo obrazové analýzy [56].…”