Abstract 2233: PI3K/Akt/mTOR signaling and plasma membrane proteins are implicated in responsiveness to adjuvant dendritic cell vaccination for metastatic colorectal cancer
| Autor: | Richard J. Barth, Stephanie Her, Jinyoung Byun, David C. Qian, Christopher I. Amos, Xiangjun Xiao, Arief A. Suriawinata |
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| Rok vydání: | 2016 |
| Předmět: | |
| Zdroj: | Cancer Research. 76:2233-2233 |
| ISSN: | 1538-7445 0008-5472 |
| Popis: | Purpose: We have previously demonstrated that metastatic colorectal cancer patients who exhibit immune responses to a dendritic cell (DC) vaccine have superior recurrence-free survival following surgery, compared to patients in whom immune responses do not occur. We sought to characterize the patterns of T lymphocyte infiltration and somatic mutations in metastases that are associated with and predictive of response to the DC vaccine. Methods: Cytotoxic, memory, and regulatory T cells in resected metastases and in surrounding normal liver tissue from 22 patients (11 responders and 11 non-responders) were enumerated by immunohistochemistry prior to vaccine administration. In conjunction with tumor sequencing, the Combined Multivariate and Collapsing method was used to identify gene mutations that are associated with vaccine response. We also derived a response prediction score for each patient using his/her tumor genotype data and variant association effect sizes computed from the other 21 patients; greater weighting was placed on genes that encode plasma membrane proteins. Results: There was no relationship between vaccine response and intra-tumor, peri-tumor, or hepatic densities of T cell subpopulations. Associated genes were found to be statistically enriched in PI3K, Akt, and mTOR signaling pathways (P < 0.001). With respect to prediction, applying a consistent score cutoff over the 22 rounds of leave-one-out cross-validation correctly inferred vaccine response in 21 of 22 patients (95%). Conclusions: Adjuvant dendritic cell vaccination has shown promise as a form of immunotherapy for patients with metastatic colorectal cancer. Its efficacy may be influenced by somatic mutations that affect pathways involving PI3K, Akt, and mTOR, as well as neoantigens on tumor cell surfaces. Citation Format: David Qian, Jinyoung Byun, Xiangjun Xiao, Stephanie Her, Arief Suriawinata, Christopher Amos, Richard Barth. PI3K/Akt/mTOR signaling and plasma membrane proteins are implicated in responsiveness to adjuvant dendritic cell vaccination for metastatic colorectal cancer. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2233. |
| Databáze: | OpenAIRE |
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