SummaryShigella sonnei is a bacterial pathogen and causative agent of bacillary dysentery. It deploys a type III secretion system to inject effector proteins into host epithelial cells and macrophages, an essential step for tissue invasion and immune evasion. Although the arsenal of bacterial effectors and their cellular targets have been studied extensively, little is known about the prerequisites for deployment of type III secreted proteins during infection. Here, we describe a novel S. sonnei adhesin, SSO1327 which is a multivalent adhesion molecule (MAM) required for invasion of epithelial cells and macrophages and for infection in vivo. The S. sonnei MAM mediates intimate attachment to host cells, which is required for efficient translocation of type III effectors into host cells. SSO1327 is nonredundant to IcsA; its activity is independent of type III secretion. In contrast to the up-regulation of IcsAdependent and independent attachment and invasion by deoxycholate in Shigella flexneri, deoxycholate negatively regulates IcsA and MAM in S. sonnei resulting in reduction in attachment and invasion and virulence attenuation in vivo. A strain deficient for SSO1327 is avirulent in vivo, but still elicits a host immune response.

Local radiotherapy is the major therapeutic approach to control inoperable cervical cancer. In this study, we analyzed the local immune microenvironment of cervical cancer before and after clinical radiation therapy to investigate whether tumor response due to immunomodulation. A total of 59 patients with pathologically diagnosed cervical cancers classified according to the International Federation of Obstetrics and Gynecology (FIGO) criteria were recruited. The patients were treated according to their disease status with standard radiation regimens. For each patient, tumor biopsies were conducted before, during and after radiation treatment with the doses of 0, 10, 20 and 30 Gy, respectively. All of the tumor samples were then grouped according to the doses delivered and tumor infiltrating lymphocytes with the biomarkers of CD8, CD4, FOXP3 and OX40 were measured by in situ immunohistochemistry. We found that before radiation treatment both CD8(+) T cell and CD4(+) T cell infiltrates were more present in the tumor stroma than in the tumor nests, while OX40(+) and FOXP3(+) T cell infiltrates were present at similar levels in both the tumor nests and stroma. After radiation treatment, the levels of CD8(+) T cells and CD4(+) T cells in the tumor nests and stroma were decreased compared with the levels before irradiation. However, OX40(+) T cells and FOXP3(+) T cells did not show any difference before and after irradiation, which indicates that the FOXP3(+) T cells were more resistant to ionizing radiation than were the cytotoxic effector T cells and demonstrates a dynamic rebalance of infiltrating lymphocytes in the tumor milieu occurs after radiotherapy. This suggest that local antitumor immunity could be compromised due to decreased cytotoxic effector cells and the relatively stable status of FOXP3(+) T cells after irradiation. Therefore, regulation of these FOXP3(+) T cells may be a potentially effective approach to enhance the efficacy of cancer radiation therapy.

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A number of reports have identified HPV DNA in breast cancer specimens and HPV type 16, 18, 31, 33, 45, and 51 were more prevalent. HPV 58 was frequently detected in cervical cancer in Shaanxi China. The aim of the present study was to investigate whether HPV 58 present in breast cancer. 169 cases of breast cancer samples and 83 benign breast lesions were analyzed. Type specific primers and oligonucliotide probe were used for the detection of HPV 58 by conventional PCR and in situ hybridization techniques. The HPV 58 viral load were measured by qPCR. p16 protein expression were evaluated by immunohistochemistry. HPV 58 E7 DNA was detected in 25 out of 169 formalin fixed paraffin embedded breast cancer tissues (14.79%) by PCR, only 1 out of 83 non-malignant breast lesions showed positive (1.20%). The results of ISH showed that 17 out of 169 (10.06%) malignant samples were positive for HPV 58 E7, and only 1 out of 83 non-malignant lesions was positive. Positive p16 immunostaining was observed in all the HPV 58 E7 ISH positive cases, but 16 out of 98 cases with HPV negative were p16 positive. The presence of HPV 58 in both normal duct epithelial cells and carcinoma in situ along with its presence in the cancer cells of the same specimen indicated the possible causal role of HPV 58 in breast cancer. The findings provide a solid morphological evidence of the involvement of HPV 58 in breast cancer development.