Abstract
BackgroundRegulatory and cytotoxic T cells are key players in the host's anticancer immune response. We studied the spatial distribution of FoxP+ and CD8+ cells to identify potential interactions.MethodsIn 202 patients 103 pre-radiochemotherapy biopsies and 153 post-radiochemotherapy tumour specimens of advanced rectal cancer were available and an immunohistochemical double staining of FoxP3+ and CD8+ tumour-infiltrating lymphocytes was performed to investigate cell density and cell-to-cell distances.ResultsFoxP3+ cells decreased after radiochemotherapy by a factor of 3 while CD8+ cells remained nearly unchanged. High epithelial (p=0.033) and stromal (p=0.009) FoxP3+ cell density was associated with an improved overall survival. Cell-to-cell distances of randomly distributed cells were simulated and compared to observed cell-to-cell distances. Observed distances shorter than the simulated, random distances were hypothesized to represent FoxP3+ cells actively interacting with CD8+ cells. Epithelial short distances were associated with a favourable prognosis while the opposite was true for the stromal compartment.ConclusionThe analysis of cell-to-cell distances may offer a tool to predict outcome, maybe by identifying functionally active, interacting infiltrating inflammatory cells in different tumour compartments.
Highlights
In recent years the significance of inflammatory cells in cancer therapy has become a central interest of research
FoxP3+ cells decreased after radiochemotherapy by a factor of 3 while CD8+ cells remained nearly unchanged
High epithelial (p=0.033) and stromal (p=0.009) FoxP3+ cell density was associated with an improved overall survival
Summary
In recent years the significance of inflammatory cells in cancer therapy has become a central interest of research. It is assumed that tumour infiltrating inflammatory cells (TIC) influence the patientsprognoses as key players in the intratumoural immune microenvironment. Antigen presenting cells initiate and shape the immune response, cytotoxic cells kill cancer cells and regulatory cells modulate the immune system and can impair the anti-tumoural immune response. The concept of immunosurveillance proposes that cancer cells can only survive when they either escape immune recognition or generate an immunosuppressive environment [3]. Tregs can suppress immune response by both cytokines and cell-to-cell www.impactjournals.com/oncotarget contact [5]; they downregulate activation, proliferation and effector functions in CD4+ T cells, CD8+ CTL, natural killer and natural killer T cells, B cells and antigen-presenting cells [6]. Tregs and CTL are counteractors promoting tumour escape and immunosurveillance, respectively. Regulatory and cytotoxic T cells are key players in the host’s anticancer immune response. We studied the spatial distribution of FoxP+ and CD8+ cells to identify potential interactions
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