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Background & Aims CD8 + T cells that produce interleukin (IL)-17 (Tc17 cells) promote inflammation and have been identified in tumors. We investigated their role in the pathogenesis of gastric cancer. Methods We used flow cytometry analyses to determine levels and phenotype of Tc17 cells in blood and tumor samples from 103 patients with gastric cancer. We performed multivariate analysis to identify factors associated with overall survival using the Cox proportional hazards model. CD8 + T cells and monocytes were isolated and cocultured in an assay for induction of Tc17 cells. Tumor cells and myeloid-derived suppressor cells (MDSCs) were isolated and used in assays of Tc17 cell function. Results Tc17 cells with distinct cytokine and functional profiles were found in gastric tumor samples from patients. The percentage of Tc17 cells increased with tumor progression and was associated with overall survival time. Tumor-activated monocytes secreted IL-6, IL-1β, and IL-23, which promoted development of Tc17 cell populations. Supernatants from cultured Tc17 cells induced production of the chemokine CXCL12 by tumor cells; this promoted CXCR4-dependent migration of MDSCs and impaired functions of anti-tumor CD8 + cytotoxic T cells via a cell contact–dependent mechanism. Conclusions Percentages of Tc17 cells in gastric tumors are associated with survival times of patients. These cells promote chemotaxis of MDSCs, which might promote tumor progression.

Development of Helicobacter pylori vaccine would be a new effective strategy for prevention and treatment of H. pylori infection. Recombinant H. pylori vaccine comprising a single subunit antigen can only induce immune response with limited protection efficiency. In this study, the protective effect of H. pylori multicomponent vaccines consisting of three recombinant subunit antigens was investigated using the Mongolian gerbil model.Mongolian gerbils were immunized with different formulations of three recombinant H. pylori antigens (UreB, HspA, and HpaA) with two different adjuvants (Al(OH)3, LT(R72DITH)) by intragastric (i.g.) or intramuscular (i.m.) routes. The protective effects of multicomponent vaccines were assessed after H. pylori challenge in different studies. The specific IgG antibodies in serum were monitored by ELISA, and the mRNA expressions of IL-4 and IFN-gamma in spleen tissue were detected by reverse transcribed polymerase chain reaction (RT-PCR).The protective effect against H. pylori challenge in gerbils immunized with three recombinant antigens and LT(R72DITH) or Al(OH)3 was significantly higher than that in single- or double-antigen vaccine-immunized and control gerbils. Furthermore, the protective effect of the triple-antigen vaccine combined with the LT(R72DITH) adjuvant (average 86.3%) was significantly greater than that of vaccine combined with the Al(OH)3 adjuvant (average 53.4%). After the first immunization, the anti-UreB/HspA/HpaA serum IgG level in gerbils immunized with triple-antigen vaccine combined with Al(OH)3 was higher than that in gerbils immunized with the vaccine combined with LT(R72DITH). Splenic interferon (IFN)-gamma and interleukin (IL)-4 transcript levels were significantly increased in LT(R72DITH) vaccine-immunized gerbils as compared to the Al(OH)3 vaccine group. Moreover, splenic IL-4 mRNA levels were higher than IFN-gamma in gerbils immunized with triple-antigen vaccine with either LT(R72DITH) or Al(OH)3.This study indicated that the recombinant multicomponent vaccine provided effective protection against H. pylori infection as compared to the single-antigen vaccine. This protective immunity would be closely associated with a predominant Th2-type response.

Helicobacter pylori, an etiological agent of gastroduodenal diseases, undergoes drastic morphological transition from spiral shape to coccoid form under oxidative stress. However, the knowledge of the specific expression profile in response to oxidative stress is relatively limited. Here, we report global proteomic analysis of H. pylori coccoids under oxidative stress. Two-dimensional gel electrophoresis analysis of H. pylori featuring coccoid revealed that 10 unique protein spots exhibit different expression profiles with comparison of that under normal microaerophilic condition. In total, seven proteins including superoxide dismutase, alkyl hydroperoxide reductase, urease G, and so forth were confirmed using matrix-assisted laser desorption/ionization time-of-flight/mass spectroscopy and then validated by reverse transcription-polymerase chain reaction, indicating that they play key roles in the physiological adaptation mechanisms of H. pylori to oxygen challenge. These data provide preliminary insights into H. pylori on coccoid generation under oxidative stress.

To study adaptive protein variation of H. pylori after colonization in Mongolian gerbils, Firstly, Clinical isolated strain M0 of H. pylori were inoculated into Mongolian gerbils and acclimated through serial passages in vivo for procuring an adaptive colonization H. pylori strain. Then, two-dimensional electrophoresis (2-DE) and mass spectrometry (MS) was taken to separate and identify the global proteins significantly changed between H. pylori strain M0 and the adaptive strain. Through serial passages the infectious rate increased from about 2/10 to 9/10 and a adaptive colonization strain M13 has been obtained. Comparative proteomic technology display that the proteinogram of H. pylori have changed after colonization in gerbils. Out of 5 differential protein spots cut out of gels for MALDI-TOF-MS identification, 4 spots were successfully identified, among which, Icd, RfaD and HP0318 were significantly higher in M13 compared with M0, while only HypB were found in M13. So far, HP0318 is a conserved hypothetical protein. These proteins may be important factors of H. pylori for adaptive colonization.