Regulatory T cells and cytotoxic T cells close to the epithelial–stromal interface are associated with a favorable prognosis

Abstract

Cytotoxic T cells and regulatory T cells play a crucial role in the outcome of cancer patients. Besides the density of these cells, it was shown recently that the spatial distribution is equally important. Here, we specifically analyzed the spatial distribution of these T cell subtypes at the epithelial-stromal interface in a rectal cancer cohort and its relevance for prognosis. We studied a cohort of 191 patients with advanced rectal cancer treated by radiochemotherapy (RCT). Tissue microarrays were immunohistochemical double-stained by FoxP3+ and CD+. Cell densities were analyzed in the stromal and epithelial compartment. Additionally, an image analysis software calculated the distances of lymphocytes to the epithelial-stromal interface (ESI). CD8+ and FoxP3+ cell counts decreased clearly after RCT with the decrease of FoxP3+ being more pronounced than of CD8+ cells. In the invasive front, short distances of the ESI to CD8+ and to FoxP3+ cells were associated with improved overall survival. Cell counts in the stromal compartment had no influence on prognosis. No correlation between stromal and epithelial lymphocyte densities was observed. The distance of epithelial-stromal interface to CD8+ and FoxP3+ cells was more accurate in predicting prognosis in the stromal compartment of rectal cancer patients than mere cell counts and could thereby be means of better stratifying patients for therapy. This observation will have to be validated in future prospective studies with regard to other tumor entities and its implications for the responsiveness of tumors to new therapeutic modalities.

Interspatial Distribution of Tumor and Immune Cells in Correlation with PD-L1 in Molecular Subtypes of Gastric Cancers

“…This is plausible, as the cytotoxic function and signaling of CD8+ lymphocytes requires their proximity to their target cells and is supported by a statistically stronger association of the intra- vs. peri- and intratumoral CD8+ lymphocytes with lower pT and pN categories in our study. The relevance of this spatial relationship has been shown in different tumors, including GCs, and is supported by our data [ 29 , 30 ]. As PD-L1 itself is an imperfect biomarker for response prediction in GCs, the analysis of the tumor microenvironment, including TILs, has been investigated in a few studies.…”

The Prognostic Value of FoxP3+ Tumour-Infiltrating Lymphocytes in Rectal Cancer Depends on Immune Phenotypes Defined by CD8+ Cytotoxic T Cell Density

“…Tissue samples were obtained from surgical resection specimens after neoadjuvant treatment ( Figure 1 ). The prognostic relevance of FoxP3+ and CD8+ T cell densities in general, cell-to-cell distances and distances to the epithelial-stromal interface have previously been reported in this cohort ( 15 , 16 ).…”

Deep learning-based tumor microenvironment segmentation is predictive of tumor mutations and patient survival in non-small-cell lung cancer

“…3m). In contrast, ‫ݐ‬ ூெெோ and ‫ݐ‬ ெூா features were associated with a decreased death hazard and therefore longer survival (Fig 3m), in line with the established role of the immune system as a barrier against tumor progression 4,19,50 . Among mutation features, TP53 and STK11 mutations significantly increased (p < 0.05, Wald test, two-sided) the death hazard, in agreement with the results of the independent Kaplan-Meier analysis (Supplementary Fig.…”