Regular and Young Investigator Award Abstracts最新文献

{"title":"973 Extrafollicular expansion and differentiation of b cells drives anti-tumor responses in metastatic cancer","authors":"Noor Nader, Dongyan Liu, H. Kim, A. Ruffin, S. Kunning, Xiaron Zhang, Daniel Dunlap, R. Semaan, R. Dhupar, A. Soloff, T. Bruno","doi":"10.1136/jitc-2022-sitc2022.0973","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0973","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"5 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125336162","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"456 Patterns and outcomes of palliative radiation therapy with immunotherapy in recurrent or metastatic head and neck squamous cell carcinoma","authors":"L. Roof, A. Yalamanchali, D. Buchberger, S. Campbell, S. Koyfman, N. Woody, N. Silver, J. Geiger, E. Yilmaz","doi":"10.1136/jitc-2022-sitc2022.0456","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0456","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125376396","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"810 Novel renal cell carcinoma immunotherapy combining TLR9-targeted STAT3 antisense oligonucleotide with PD-1 blockade","authors":"Marice B. Alcantara, A. Chehrazi-Raffle, N. Dizman, W. Tang, L. Meza, Z. Zengin, Dongfang Wang, D. Moreira, Alan Horsager, J. Hsu, S. Pal, M. Kortylewski","doi":"10.1136/jitc-2022-sitc2022.0810","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0810","url":null,"abstract":"Background therapy combinations utilizing PD-1 immune checkpoint inhibition have improved outcomes in patients with RCC; however, positive clinical responses are limited to select individuals. 1 Various studies indicate resistance is mediated partly through STAT3 induced activity and a concomitant accumulation of tumor infiltrating myeloid derived suppressor cells and tumor promoting M2 macrophages capa-ble of suppressing anti-tumor responses independent of PD-1 signaling. 2 Indeed, in a separate study, we observed an increase in cytokines IL-6, IL-8 and persistent STAT3 activity within myeloid cells in RCC patients with resistance to anti-PD-1/CTLA-4 therapy. In this preclinical study, we investigated a novel treatment strategy combining anti-PD-1 therapy with our original CpG-STAT3ASO oligonucleotide strategy to knockdown STAT3 specifically within TLR9-positive myeloid cell populations associated with RCC tumors. Methods 6-8 were subcuta-neously with 500,000 in were using (IV, together with anti-PD-1 (IP, con-trol only Immune alterations in and tumor-draining lymph nodes were assessed via spectral cytometry. Statistical significance was determined using two-way ANOVA or Wilcoxon signed ranked test with SEM. Results CpG-STAT3ASO with anti-PD-1 significantly inhibited growth of syngeneic Renca tumors compared to either treatment alone or negative controls. To elucidate the immune-mediated mechanisms underpinning this efficacy, we undertook spectral cytometry analysis of tumor and tumor draining lymph nodes. In comparison to PBS, IgG and anti-PD-1 alone, combination CpG-STAT3ASO and anti-PD-1 treatment induced maturation and activation of intratumoral dendritic cells (DCs) macrophages, including a decrease in immunosuppressive M2 macrophages, with a concomitant increase in anti-tumor M1 an increase in intratumoral CD8+ T cells, decrease in CD4+ Tregs and increase CD8+ T cell to Treg ratios. In fact, anti-PD-1 alone treated cohorts was shown to have high percentages of alternatively activated (pro-tumor) M2 macrophages in comparison to combination treated cohorts where an increase in anti-tumor M1 macrophages was observed. This suggests anti-PD-1 alone efficacy may be limited by its failure to induce maturation/activation of myeloid cells. Our results indicate that combination of PD1 blockade with systemic administration of CpG-STAT3ASO significantly improves antitumor efficacy against the tested kidney cancer model in comparison to each treatment alone. The improved treatment efficacy is likely related to more potent activation and reprogramming of tumor-associated myeloid cells, particularly macrophages. Our results warrant further investigation into myeloid cell specific STAT3 silencing in combination with Anti-PD-1 in RCC.","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"125381224","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"614 Microbiome modification with fecal microbiota transplant from healthy donors before anti-PD1 therapy reduces primary resistance to immunotherapy in advanced and metastatic melanoma patients","authors":"B. Routy, J. Lenehan, Brendan A. Daisley, M. Messaoudene, K. Al, C. Richard, Wilson H. Miller, R. Jamal, Scott Ernst, Diane Logan, K. Bélanger, Luara Martinez- Gili, B. Mullish, P. Takis, Cecilia Hermosilla Samayoa, M. Ninkov, S. Parvathy, C. Lambert, A. Elkrief, R. Lapointe, M. Haeryfar, J. Burton, Michael Silverman, Saman Maleki","doi":"10.1136/jitc-2022-sitc2022.0614","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0614","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"163 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126945876","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"409 Manufacturing of a clinical scale CD8 TIL product, AGX148, with and without gene silencing of PD-1 using self-delivering RNAi INTASYLTMPH-762","authors":"C. Thalhofer, S. Fricker, Ryan Montler, E. Ballinger, Nick Morris, Jake Moses, D. Yan, T. Moudgil, Bernard A Fox, Nelson Sanjuan, Eric Tran, J. Cardia, A. Weinberg","doi":"10.1136/jitc-2022-sitc2022.0409","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0409","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"183 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"127041767","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"140 Assessment of differences in tumor mutational burden identified on liquid biopsy in 16,870 patients newly diagnosed with metastatic cancer","authors":"Eugene Kwon, Daniel S. Childs, B. Stish, S. Boorjian, M. Tollefson, C. Britton, A. Mahmoud, Angela Thompson, R. Barnett, L. Drusbosky, L. Bucheit","doi":"10.1136/jitc-2022-sitc2022.0140","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0140","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"34 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115195917","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"963 Significantly different immune microenvironment between triple-negative breast cancer with and without neoadjuvant chemotherapy through multiplex immunohistochemistry","authors":"Miseon Lee, Hyun Lee, G. Gong, H. Lee","doi":"10.1136/jitc-2022-sitc2022.0963","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0963","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"272 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115210455","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"34 Neutrophil-to-eosinophil ratio as a biomarker for clinical outcomes in advanced stage melanoma patients treated with anti-PD-1 therapy","authors":"V. Pozorski, Yeonhee Park, Dahlia Tesfamichael, Y. Mohamoud, Vincent T. Ma","doi":"10.1136/jitc-2022-sitc2022.0034","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0034","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"9 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115565985","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1399 ZL 1218 targets the most suppressive intratumoral Treg subpopulation to avoid peripheral toxicities","authors":"Jing Zhang, Linda Liu, Grace Wang, Joshua Zeng, Tao Geng, Chakrapani Tripathi, Lei Wang","doi":"10.1136/jitc-2022-sitc2022.1399","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.1399","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"108 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115569790","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"909 Overcoming resistance to NK-mediated lysis in enzalutamide-resistant prostate cancer cells","authors":"Madeline Dahut, Kristen Fousek, Lucas A Horn, Haiyan Qin, J. Schlom, C. Palena","doi":"10.1136/jitc-2022-sitc2022.0909","DOIUrl":"https://doi.org/10.1136/jitc-2022-sitc2022.0909","url":null,"abstract":"","PeriodicalId":398566,"journal":{"name":"Regular and Young Investigator Award Abstracts","volume":"260 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2022-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"116210769","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}