Onathan Schneck ([email protected]) Journal for ImmunoTherapy of Cancer 2018, six(Suppl 1):P570 Background Even though recent

Onathan Schneck ([email protected]) Journal for ImmunoTherapy of Cancer 2018, six(Suppl 1):P570 Background Even though recent studies have shown a vital role in the microbiome in modulating anti-tumor immune responses, its mechanism remains unclear. A single proposed mechanism is as a consequence of cross-reactivity in between antigens expressed in commensal bacteria and neoepitopes EphA5 Proteins medchemexpress identified in tumors. We have identified a cross-reactive antigen expressed in commensal bacteria Bifidobacterium (Bifido) “SVYRYYGL” (henceforth called SVY) and show that it conveys a neoantigen-specific cross-reactivity towards the classic neoantigen “SIY.” Solutions The SVY-specific response was analyzed by way of biophysical experiments and molecular dynamics simulations to decide antigen processing and MHC binding. T cell expansion studies from SIY and SVY T cell populations in addition to cross specificity studies reveals the cross-reactive T cell populations. B6 mice housed from Jackson, Bifido colonized mice, and Taconic, Bifido lacking, mice were applied for examine Bifido colonization on T cell expansion. Sorting crossreactive T cell populations from Bifido good or unfavorable mice according to antigen specificity and T cell receptor (TCR) beta sequencing permits to examine the impact of colonization on TCR repertoire composition. Finally the anti-tumor activity on the commensal bacteria population against the cross- reactive tumor antigen was tested by adoptive transfer research with B16-SIY melanoma model. Benefits The SVY-specific response benefits from SVY peptide binding the H2Kb MHC and may be processed from whole bacteria. The commensal bacteria SVY-specific T cells population features a cross-reactive SIYspecific T cell response and can Kininogen-1 Proteins custom synthesis recognize tumors expressing the “SIY” antigen. Mice lacking Bifido possess a decreased SVY-specific T cell response and an altered (TCR) repertoire when compared with Bifido. colonized animals. Bifido. colonization not just shapes the SVY-specific TCR repertoire but selects for clones which are represented inside the SIY TCR repertoire. Cross- reactive SVY-specific T cells recognize tumors bearing SIY in vivo in an adoptive T cell transfer model of murine melanoma and results in decreased tumor development and extended survival. Conclusions Our operate demonstrates that commensal bacteria can directly stimulate anti-tumor immune responses via T cell cross-reactivity and delivers a proof of principle for how bacterial antigens can shape the Tcell landscape. P571 Targeted sequencing of 16s rRNA Gene to know the diversity and composition with the gut microbiome Rajesh Gottimukkala, MS1, Jianping Zheng2, Karen Clyde, PhD2, Fiona Hyland2, Janice Au-Young, PhD2 1 ThermoFisher Scientific, Fremont, CA, USA; 2Thermo Fisher Scientific, south san francisco, CA, USA Correspondence: Rajesh Gottimukkala ([email protected]) Journal for ImmunoTherapy of Cancer 2018, six(Suppl 1):P571 Background Current research in humans and experiments in mouse models demonstrated the important function on the gut microbiota in modulating the tumor response to check point blockade immunotherapy. 1 studyshowed an association in between damaging outcome working with CTLA-4 blockade therapy plus the absence of a distinct gut microbiome. So, the gut microbiota has emerged as a promising biomarker to assess the efficacy of immune-modulatory drugs. Next generation sequencing in the 16S rRNA Gene is widely made use of as common for understanding the composition with the gut microbiome. Methods The AmpliSeq pan-Bacterial Analysis pan.