Background Tumor-infiltrating lymphocytes (TILs) have recently been reported as an important factor in the tumor microenvironment and influence the growth and progression of cancer. However, the relationship between immune cell subpopulations, such as CD4+, CD8+, and FOXP3+, in breast cancer, especially in triple negative carcinoma (TNC), remains unclear. Methods The subjects were 107 patients with TNC that were surgically resected at Dokkyo Medical University Hospital between 2006 and 2018. The expression of CD4+, CD8+, and FOXP3+ was evaluated in TILs and expressed as the numbers of positive cells. Results Univariate analysis revealed that the TILs were not prognostically significant. In multivariate analyses, increased infiltration of intratumoral (i) CD4+ TILs was found to have a good prognosis in relapse-free survival (RFS). In contrast, a high stromal CD8+ TILs level was found to be a favorable prognostic factor in RFS (p = 0.038) and overall survival (OS) (p = 0.046). A low sFOXP3 + TILs level was significantly associated with favorable RFS (p < 0.001) and OS (p = 0.029). Conclusions The present study demonstrated no difference in TILs and survival in TNC. However, there was a significant correlation in prognosis with levels of iCD4+, sCD8+, and sFOXP3 + TILs in TNC. The difference in TNC clinical outcome may be due to the subtype of the infiltrating TILs.

No abstract

No abstract

Using a mouse model, we investigated the mechanisms of heterogeneity in response to ionizing radiation in this research. C57BL/6J and C3H/HeMs mice were irradiated with gamma rays at 10 and 20 Gy. The animals were sacrificed at times corresponding to the latent period, the pneumonic phase, and the start of the fibrotic phase for histological investigation. Small areas of fibrosis initially appeared in C57BL/6J mice at 4 weeks postirradiation with 20 Gy, whereas small inflammatory lesions appeared at 4 and 8 weeks after 20 and 10 Gy, respectively. The alveoli septa were thickened by an infiltration of inflammatory cells, and alveoli were obliterated in lungs from C57BL/6J mice after 20 Gy irradiation. At 24 hours and from 2 to 4 weeks postirradiation, fourfold more CD44 positive cells had accumulated in the lungs of C3H/HeMs than in C57BL/6J mice. Hyaluronan accumulated 12 hours after irradiation, and the rapid resolution was achieved within 2 weeks in the lungs in both strains of mice. C57BL/6J mice lungs accumulated dense collagen at 8 weeks. Quantitative RT-PCR assay was performed for several genes selected by cDNA microarray analysis. The expression of several genes, such as Cap1, Il18, Mmp12, Per3, Ltf, Ifi202a, and Rad51ap1 showed strain-dependent variances. In conclusion, a histological investigation suggested that C3H/HeMs mice were able to induce a more rapid clearance of matrix after irradiation than C57BL/6J mice. The expression analysis showed that the several genes are potentially involved in interstrain differences in inflammatory response causing radiation-induced lung fibrosis.

Published reports about skin reactions to radiotherapy, especially among breast-cancer patients, suggest that there are interindividual differences in the normal tissue response, and genetic factors are thought to be involved in this variation. An analysis of murine strain differences may reveal the mechanism of genetic factors in the extent of normal tissue damage from irradiation for several endpoints. The variation in the radiation susceptibility was observed when the skin of mice from strains A/J, C3H/HeMs, C57BL/6J, C.B.17/Icr-scid and C3H-scid was irradiated with a single dose ranging from 10 to 60 Gy, using Cs-137 gamma rays. The active skin reaction of A/J mice lasted for months. C3H/HeMs mice showed dose-dependent skin damage, and consequently recovered to a state of mild damage within 40 days after local irradiation. The time course of the response in C57BL/6J mice was shorter than in A/J mice. The 2 strains of scid mice exhibited severe damage after irradiation at any dose from 20 to 50 Gy, and did not show any dose dependency. The variation between murine strains in macroscopic and histopathological changes in skin during the progression and resolution of damage caused by irradiation suggests an inter-strain variation in the expression of genes involved in injury, apoptosis, repair, and remodeling.