Histological differentiation impacts the tumor immune microenvironment in gastric carcinoma: Relation to the immune cycle.

BACKGROUND: Various histological types of gastric carcinomas (GCs) differ in terms of their pathogenesis and their preexisting background, both of which could impact the tumor immune microenvironment (TIME). However, the current understanding of the immune contexture of GC is far from complete. AIM: To clarify the tumor-host immune interplay through histopathological features and the tumor immune cycle concept. METHODS: In total, 50 GC cases were examined (15 cases of diffuse GC, 31 patients with intestinal-type GC and 4 cases of mucinous GC). The immunophenotype of GC was assessed and classified as immune desert (ID), immune excluded (IE) or inflamed (Inf) according to CD8+ cell count and spatial pattern. In addition, CD68+ and CD163+ macrophages and programmed death-ligand 1 (PD-L1) expression were estimated. RESULTS: We found that GCs with different histological differentiation demonstrated distinct immune contexture. Most intestinal-type GCs had inflamed TIMEs rich in both CD8+ cells and macrophages. In contrast, more aggressive diffuse-type GC more often possessed ID characteristics with few CD8+ lymphocytes but abundant CD68+ macrophages, while mucinous GC had an IE-TIME with a prevalence of CD68+ macrophages and CD8+ lymphocytes in the peritumor stroma. PD-L1 expression prevailed mostly in intestinal-type Inf-GC, with numerous CD163+ cells observed. Therefore, GCs of different histological patterns have specific mechanisms of immune escape. While intestinal-type GC was more often related to PD-L1 expression, diffuse and mucinous GCs possessing more aggressive behavior demonstrated low immunogenicity and a lack of tumor antigen recognition or immune cell recruitment into the tumor clusters. CONCLUSION: These data help to clarify the links between tumor histogenesis and immunogenicity for a better understanding of GC biology and more tailored patient management.

Mechanisms of the Impact of Hashimoto Thyroiditis on Papillary Thyroid Carcinoma Progression: Relationship with the Tumor Immune Microenvironment.

BACKGROUND: The relationship between Hashimoto thyroiditis (HT) and papillary thyroid carcinoma (PTC) remains uncertain. We assessed the impact of HT on the tumor immune microenvironment (TIME) in PTC. METHODS: Thirty patients with PTC (group 1) and 30 patients with PTC and HT (group 2) were enrolled in this pilot study. The distribution and number of CD8+ lymphocytes, plasma cells (CD138+), regulatory T cells (forkhead box P3 [FOXP3+)], mast cell tryptase (MCT+), and M2 macrophages (CD163+) were evaluated. To test the hypothesis that HT impacts PTC development via signal transducer and activator of transcription 6 (STAT6) activation and M2 macrophage polarization, we investigated STAT6 expression in tumor and stromal cells. We also evaluated vascular endothelial growth factor (VEGF) expression by lymph node metastasis (LNM) status. RESULTS: TIME showed significant between-group differences. Group 1 patients demonstrated immune desert or immune-excluded immunophenotypes, while an inflamed phenotype with more CD8+ cells (P<0.001) predominated in group 2. Immune-excluded TIME was associated with the highest LNM rate. In PTC, LNM was associated with more numerous CD163+ cells. Moreover, LNM in group 1 was associated with increased numbers of mast cells peritumorally and FOXP3+ cells intratumorally and peritumorally. Group 2 demonstrated higher STAT6 but not higher VEGF expression in tumor cells. High VEGF expression was associated with LNM regardless of HT status. CONCLUSION: Concomitant HT impacted PTC signaling via STAT6 and TIME by increasing the number of CD8+ cells. LNM is associated with increases in CD163+ cells and VEGF expression in PTC, whereas HT affected LNM through different mechanisms.

Hashimoto's thyroiditis attenuates progression of papillary thyroid carcinoma: deciphering immunological links.

Although some studies have investigated the clinicopathologic relationships between papillary thyroid carcinoma (PTC) and Hashimoto's thyroiditis (HT), there is still no clear understanding of differences in tumor immune microenvironment for PTC with coexisting HT and HT effect on PTC progression. The aim of this study was to clarify immune-mediated mechanisms of coexisting HT, which might influence PTC progression. 30 patients with histologically confirmed conventional-type PTC and 30 patients with PTC and coexisting HT were enrolled in the study. To analyze the role of immune-mediated links between PTC and HT, immunohistochemical investigation was conducted to count the number of different immune cells including T-cytotoxic cells (CD8), plasma cells (CD138), Treg cells (FOXP3), mast cells (MCT), and M2 macrophages (CD163). It was shown that despite the high number of immune cells in the intact thyroid tissues of PTC patients with coexisting HT there were no significant differences in M2 macrophages, mast cells and Treg counts inside PTC with or without HT. PTC with HT was associated with a higher number of CD8+ cells (P < 0.001) reflecting the ability of immune system to generate and recruit T-cytotoxic cells in tumor area, which can explain the protective effect of HT on PTC progression. Lymph node metastases development was associated with an increased number of mast cells, M2 macrophages and Treg along with a decreased plasma cells count regardless of coexisting HT. However, we did not find significant differences in T-cytotoxic cells quantity in node-positive and node-negative patients with or without HT, which encourages further investigation of immune escape mechanisms in PTC.