The tumor-infiltrating effector regulatory T cell:CD8+ lymphocyte ratio in invasive breast cancer

Background Tumor-infiltrating lymphocytes (TILs) in breast cancer comprise immunostimulating and immunosuppressive components. Although FOXP3+ TILs are prototypical immunosuppressive TILs, only effector regulatory T cells (eTreg), a subset of immunosuppressive FOXP3+ TILs, are undetectable on immunohistochemical staining. This study aimed to evaluate the immunosuppressive potential of eTregs and the role of prototypical immunostimulatory CD8+ TILs in invasive breast cancer. Methods Fresh TILs extracted from 84 invasive breast cancer patients were analyzed via flow cytometry. We evaluated eTregs (CD4+FOXP3highCD45RA−), other FOXP3+ Treg subsets (naïve and non-Tregs), and total CD8+CD4- TILs. Clinicopathological factors, including histopathological characteristics, were also assessed. Results The median eTreg proportion of the total CD4+TILs was 18.7% (interquartile range [IQR], 16.4–25.5%); CD8+TILs, 124% (IQR, 87.5–140%). The proportion of eTregs to total FOXP3+ TILs varied (median, 65.6%; range, 10.1–93.2%). In an immunosuppression assay, only eTregs displayed potent immunosuppression; however, other Treg subsets did not. Among 39 patients who received neoadjuvant chemotherapy, eTreg subsets and pathological compete response (pCR) did not differ significantly, while pCR rates were significantly higher among individuals with a high than those with a low CD8+/eTreg ratio (90.2% vs 33.3%; P<0.05). Among all patients, a high CD8+/eTreg ratio tended to be associated with better disease-free survival rather than a low CD8+/eTreg ratio (P=0.09). Conclusions The CD8+/eTreg ratio is simple, optimal indicator of cancer immunity, and a high CD8+/eTreg ratio enhances the prognosis and treatment response in invasive breast cancer patients. However, further studies are required to validate the present findings.

Cooperate or compete? Influence of sex and body size on sheltering behaviour in the wall lizard, Podarcis muralis

Reptile sheltering behaviour, despite profound life history ramifications, remains poorly investigated. Whether or not individuals share a suitable shelter or, conversely, exclude conspecifics may depend on associated costs (resource partitioning, sexual harassment, disease or parasite contamination) and benefits (predation risk dilution, thermal resilience, information sharing). We performed two experiments on field caught wall lizards (Podarcis muralis), a highly territorial species, to investigate the relative roles of sex and body size in night sheltering. In the first experiment, random pairs of lizards were offered two identical shelters. Lizards either shared a shelter, or sheltered separately. In the second experiment, different random pairs of lizards were offered only one shelter so as to elicit a share or compete response. Body size and sex both appeared as significant drivers for sheltering patterns. Unexpectedly, wall lizards often chose to share shelters. When only one shelter (too small to accommodate two adult lizards) was available, many lizards rejected the sheltering option in preference for aggregation. Such aggregative behaviour was not sex dependant, and may reflect thermoregulatory or anti-predatory benefits. Our results nevertheless suggest that cooperative behaviour may exist in wall lizards.