Spatial distribution of FoxP3+ and CD8+ tumour infiltrating T cells reflects their functional activity

Posselt, Rebecca; Erlenbach-Wünsch, Katharina; Haas, Matthias; Jessberger, Jonas; Büttner‐Herold, Maike; Haderlein, Marlen; Hecht, Markus; Hartmann, Arndt; Fietkau, Rainer; Distel, Luitpold

doi:10.18632/oncotarget.11039

Cited by 31 publications

(41 citation statements)

References 34 publications

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“…In a previous study, pretherapeutic biopsies with high amounts of FoxP3+ cells were associated with a favorable overall survival in the stromal as well as in the intraepithelial compartment. 3 In the present study, we analyzed fewer patients than in the previous study. This may be the main reason for a lower statistical significance for the stromal cell densities in the pretherapeutic biopsies.…”

Section: Discussionmentioning

confidence: 85%

“…For analyzing the slides, an image analysis software was used (Biomas, Erlangen, Germany). 3,12,13 The outlines of the epithelial-stromal interface and TMA spot were marked and the size was calculated (mm 2 ). Cells were counted solely in the stromal compartment.…”

Section: Analysis Of the Slidesmentioning

confidence: 99%

“…Cell counts of the epithelial compartment were obtained from a previous study. 3 Counting and allocation of FoxP3+-and CD8+ T cells were performed semiautomatically. On average per patient and region, 448 FoxP3+ cells and 434 CD8+ cells were analyzed.…”

Section: Analysis Of the Slidesmentioning

confidence: 99%

“…Many studies showed that high CD8+ T cell counts in various solid tumors, e.g. renal cell carcinoma, 1 urethral carcinoma, 2 as well as colorectal carcinoma, 3 are associated with a favorable prognosis. The opposite was reported to be true for high Treg counts.…”

Section: Introductionmentioning

confidence: 99%

“…FoxP3-positive cells are associated with a favorable prognosis in patients with advanced rectal cancer. 3 In our recent study we could show that not only the count of FoxP3+ and CD8+ T cells is of major importance but also the spatial distribution of the tumor-infiltrating lymphocytes (TILs). 3 We hypothesize that cell-to-cell distances of TILs can serve as a surrogate marker of their functional activity and interaction and therefore can predict prognosis of cancer patients more accurately than mere cell counts.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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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.

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Section: Discussionmentioning

confidence: 85%

Section: Analysis Of the Slidesmentioning

confidence: 99%

Section: Analysis Of the Slidesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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

et al. 2020

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High‐dimensional analyses reveal a distinct role of T‐cell subsets in the immune microenvironment of gastric cancer

et al. 2020

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Objectives. To facilitate disease prognosis and improve precise immunotherapy of gastric cancer (GC) patients, a comprehensive study integrating immune cellular and molecular analyses on tumor tissues and peripheral blood was performed. Methods. The association of GC patients' outcomes and the immune context of their tumors was explored using multiplex immunohistochemistry (mIHC) and transcriptome profiling. Potential immune dysfunction mechanism/s in the tumors on the systemic level was further examined using mass cytometry (CyTOF) in complementary peripheral blood from selected patients. GC cohorts with mIHC and gene expression profiling data were also used as validation cohorts. Results. Increased CD4 + FOXP3 + T-cell density in the GC tumor correlated with prolonged survival. Interestingly, CD4 + FOXP3 + T cells had a close interaction with CD8 + T cells rather than tumor cells. High densities of CD4 + FOXP3 + T cells and CD8 + T cells (High-High) independently predicted prolonged patient survival. Furthermore, the interferon-gamma (IFN-c) gene signature and PDL1 expression were up-regulated in this group. Importantly, a subgroup of genomically stable (GS) tumors and tumors with chromosomal instability (CIN) within this High-High group also had excellent survival. The High-High GS/CIN tumors were coupled with increased frequencies of Tbet + CD4 + T cells and central memory CD4 + T cells in the peripheral blood. Conclusion. These novel findings identify the combination of CD8 + T cells and FOXP3 + CD4 + T cells as a significant prognostic marker for GC

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The Watch and Wait Approach After Neoadjuvant Therapy: The Australian Viewpoint

Kong

Heriot

2019

Comprehensive Rectal Cancer Care

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Spatial distribution of FoxP3+ and CD8+ tumour infiltrating T cells reflects their functional activity

Cited by 31 publications

References 34 publications

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

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

High‐dimensional analyses reveal a distinct role of T‐cell subsets in the immune microenvironment of gastric cancer

The Watch and Wait Approach After Neoadjuvant Therapy: The Australian Viewpoint

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