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.2009 Sep 4:9:65.
doi: 10.1186/1471-230X-9-65.

Stromal regulatory T-cells are associated with a favourable prognosis in gastric cancer of the cardia

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Stromal regulatory T-cells are associated with a favourable prognosis in gastric cancer of the cardia

Matthias Haas et al. BMC Gastroenterol..

Abstract

Background: Recent evidence suggests that CD4+CD25+FoxP3+ regulatory T-cells (Treg) may be responsible for the failure of host anti-tumour immunity by suppressing cytotoxic T- cells. We assessed the prognostic significance of tumour infiltrating lymphocytes (TIL) in intestinal-type gastric cardiac cancer.

Methods: Tumour infiltrating lymphocyte (TIL) subsets and tumour infiltrating macrophages (TIM) were investigated in 52 cases using tissue microarrays. The interrelationship between the cell populations (CD3+, CD8+, CD20+, CD68+, GranzymeB+, FoxP3+) in different compartments and NED-survival was investigated (median follow-up time: 61 months).

Results: Intraepithelial infiltration with TIL and TIM including Treg was generally low and not related to NED-survival. However, patients with large numbers of FoxP3+ Treg in the tumour stroma (>125.9 FoxP3+TILs/mm2) had a median survival time of 58 months while those with low FoxP3+ TIL counts (<125.9 FoxP3+TILs/mm2) had a median survival time of 32 months (p = 0.006). Patients with high versus low stromal CD68+/FoxP3+ cell ratios in primary tumour displayed median survivals of 32 and 55 months, respectively (p = 0.008).

Conclusion: Our results suggest that inflammatory processes within the tumour stroma of gastric intestinal-type adenocarcinomas located at the gastric cardia may affect outcome in two ways. Tumour-infiltrating macrophages are likely to promote carcinogenesis while large numbers of Treg are associated with improved outcome probably by inhibiting local inflammatory processes promoting carcinogenesis. Thus, inhibition of Treg may not be a feasible treatment option in gastric adenocarcinoma.

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Figures

Figure 1
Figure 1
Tissue microarrays. (A) Tissue microarray, tumor punches [TU], metastatic lymph node punches [LM] and control lymph node punches stained for CD3. (B) Primary tumor side. By means of a semi-automatic image processing software (Biomas, Erlangen, Germany), the count of positively stained cells was set into relation to the surface of the epithelial compartment [EC] (after exclusion of the luminal compartment [LC]) and the stromal compartment [SC], respectively. (C) FoxP3+TILs in primary tumor site and the stromal compartment (D) FoxP3+cells in the lymph node (E) FoxP3+cells in control lymph node (F) CD3+TILs in primary tumor site (G) CD8+TILs in primary tumor site (H) CD20+TILs in primary tumor site (I) CD68+macrophages in primary tumor site (J) Granzyme B+TILs in primary tumor site.
Figure 2
Figure 2
Mean counts of TIL-subtypes in different compartments. The counts are given per mm2. (A) CD3+counts (B) CD8+counts (C) FoxP3+counts. The asterisks (*) indicate that a statistical significant difference (p < 0.001 level) was observed between intraepithelial and stromal compartment of primary tumor and metastatic tissue of the lymph node, respectively, and between affected and uninvolved lymph node.
Figure 3
Figure 3
Prognostic significance of FoxP3+lymphocytes in gastric adenocarcinoma of the cardia. NED-survival rates in relation to the TIL infiltration were calculated by the Kaplan-Meier method and analyzed by the log-rank test. (A) Distribution of FoxP3+cell counts in stromal compartment of primary tumor. The abscissa shows the average number of intraepithelial FoxP3+TILs while the ordinate depicts the number of cases in each class. (B) Impact of FoxP3+TILs in epithelial compartment of primary tumor, (C) impact of FoxP3+TIL in stromal compartment of primary tumor, (D) impact of FoxP3+TILs in tumor compartment of metastasis, (E) impact of FoxP3+TILs in stromal compartment of metastasis, (F) impact of FoxP3+cells in lymph nodes.
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