Our results indicate that lack or reduction of HLA class I antigens and expression of APM components in ESCC may render some tumor cells to escape the immunosurveillance mediated by CD8(+) T cells and contribute to the clinical course of ESCC.

No abstract

During tumorigenesis, tumor infiltrating regulatory T (Treg) cells restrict the function of effector T cells in tumor microenvironment and thereby promoting tumor growth. The anti-tumor activity of effector T cells can be therapeutically unleashed, and is now being exploited for the treatment of various types of human cancers. However, the immune suppressive function of Treg cells remains a major hurdle to broader effectiveness of tumor immunotherapy. In this article, we reported that the deletion of Bcl6 specifically in Treg cells led to stunted tumor growth, which was caused by impaired Treg cell responses. Notably, Bcl6 is essential in maintaining the lineage stability of Treg cells in tumor microenvironment. Meanwhile, we found that the absence of follicular regulatory T (Tfr) cells, which is a result of Bcl6 deletion in Foxp3 + cells, was dispensable for tumor control. Importantly, the increased Bcl6 expression in Treg cells is associated with poor prognosis of human colorectal cancer and lymph node metastasis of skin melanoma. Furthermore, Bcl6 deletion in Treg cells exhibits synergistic effects with immune checkpoint blockade therapy. Collectively, these results indicate that Bcl6 actively participates in regulating Treg cell immune responses during tumorigenesis and can be exploited as a therapeutic target of anti-tumor immunity.

Esophageal carcinoma is one of the most common and highly aggressive malignant neoplasms in the world, particularly in China. More than 90% of esophageal cancers are ESCC.1,2) Despite advances made in surgical techniques and chemo-radiotherapy during the past several decades for the treatment of ESCC, the prognosis of ESCC remains poor with the 5-year survival rate of approximately 15%.2,3) Moreover, unresectable and relapsed esophageal cancers are still resistant to the currently available chemotherapy or radiotherapy regimens, and there is no substantial change in overall survival. The poor prognosis of esophageal cancer is due to the lack of early screening strategies, and most of patients are in advanced stage at diagnosis. As a result, its mortality rate is almost equal to its incidence in some countries.2) Consequently, there is an urgent need to develop a novel therapeutic strategy for this disease, and immunotherapy may be a promising approach for improvement of ESCC treatment. However, the tumor associated antigens that can be used as vaccine for successful ESCC immunotherapy have not been well identified, and it has been suggested that the HPV16 E7 protein could be a potential target for ESCC vaccine. 4)Epidemiological studies indicate that many factors may be associated with esophageal cancer. However, the molecular mechanisms of ESCC still remain unclear.3) Accumulating evidence has also suggested that infection with high-risk HPVs, particularly HPV type 16, has been reported as a potential risk factor for ESCC, especially at high incidence areas in China.3,5-7) The E6 and E7 oncoproteins of the highrisk HPV types can efficiently destroyed the cell cycle regulatory machinery and the apoptotic pathways by binding to a number of host-cell proteins.8) Thus, the ability of HPV oncoproteins to alter control of the cell cycle imparts growth advantage on the cells and leaves them vulnerable to other genetic changes that ultimately result in malignant transformation. Therefore, the consistent expression of E6 and E7 oncoproteins with strong immunogenicity in HPV-containing precancerous lesions and carcinomas suggests that these proteins represent attractive targets for immunotherapeutic strategies against HPV-associated malignancies.8) Additionally, circulating HPV E7 specific effector T cells were detectable in patients with squamous cell carcinoma of the oropharynx (SCCO) and in squamous cell carcinoma of the head and neck (SCCHN) patients.9,10) Indeed, the malignant transformation of human esophageal epithelial cells was also induced in vitro by high-risk E6/E7 in synergy with TPA or human telomerase reverse transcriptase (hTERT), and these cells showed many features similar to those of ESCC. 11,12) These observations supported the role of HPV in esophageal carcinogenesis. Therefore, the immunogenicity of HPV 16 E7-encoded antigen might be critical factors to developing vaccine-based strategies for enhancing antitumor immunity in patients with HPV16 E7-expressing ESCC. However, there were few reports on s...

Background There are large knowledge gaps on the transmission dynamics of Mycobacterium tuberculosis in settings where both tuberculosis and HIV are endemic. We aimed to assess the infectiousness of tuberculosis patients coinfected with HIV. Methods We systematically searched for studies of contacts of both HIV-positive and negative tuberculosis index cases. Our primary outcome was Mycobacterium tuberculosis infection in contacts. Data on sputum smear and lung cavitation status of index cases was extracted from each study to assess effect modification. Secondary outcomes included prevalent tuberculosis and HIV in contacts of HIV-positive and negative index cases. Results Of 5,255 original citations identified, 32 studies met inclusion criteria including 25 studies investigating M. tuberculosis infection (Nparticipants=36,893), 13 on tuberculosis (Nparticipants=18,853), and 12 on HIV positivity (Nparticipants=18,424). Risk of M. tuberculosis infection was lower in contacts of HIV-positive index cases (Odds Ratio [OR], 0.67, 95% CI, 0.58–0.77) but was heterogeneous (I2=75.1%). Two factors modified this relationship: the lung cavitary status of the index case and immunosuppression (measured through CD4 counts or HIV or AIDS diagnoses) among index patients living with HIV. Rates of HIV were consistently higher in contacts of coinfected index cases (OR, 4.9, 95% CI, 3.0–8.0). This was modified by whether the study was in sub-Saharan Africa (OR, 2.8, 1.6–4.9) or in another global region (OR, 9.8, 5.9–16.3). Conclusions Tuberculosis patients coinfected with HIV are less infectious than HIV-uninfected cases when they have severe immunosuppression or paucibacillary disease. Contacts of coinfected index cases are almost five times more likely to also have HIV.