Publications by authors named "W R Gillanders"

Background: Neoantigen-targeting therapies including personalized vaccines have shown promise in the treatment of cancers, particularly when used in combination with checkpoint blockade therapy. At least 100 clinical trials involving these therapies have been initiated globally. Accurate identification and prioritization of neoantigens is crucial for designing these trials, predicting treatment response, and understanding mechanisms of resistance.

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Background: Neoantigen vaccines can induce or enhance highly specific antitumor immune responses with minimal risk of autoimmunity. We have developed a neoantigen DNA vaccine platform capable of efficiently presenting both HLA class I and II epitopes and performed a phase 1 clinical trial in triple-negative breast cancer patients with persistent disease on surgical pathology following neoadjuvant chemotherapy, a patient population at high risk of disease recurrence.

Methods: Expressed somatic mutations were identified by tumor/normal exome sequencing and tumor RNA sequencing.

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To study the spatial interactions among cancer and non-cancer cells, we here examined a cohort of 131 tumour sections from 78 cases across 6 cancer types by Visium spatial transcriptomics (ST). This was combined with 48 matched single-nucleus RNA sequencing samples and 22 matched co-detection by indexing (CODEX) samples. To describe tumour structures and habitats, we defined 'tumour microregions' as spatially distinct cancer cell clusters separated by stromal components.

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Article Synopsis
  • Breast cancer (BC) has distinct molecular subtypes influenced by different cell origins, yet the transcriptional networks for these subtypes are not well understood.
  • This study utilized advanced techniques on 61 samples from 37 BC patients to reveal how gene expression and chromatin accessibility connect BC subtypes to their likely cells of origin.
  • Key transcription factors BHLHE40 and KLF5 were found to play crucial roles in luminal and basal-like tumors, respectively, and exhausted CD8 T cells were linked to immune dysfunction in basal-like BC, showcasing the potential of single-cell level analysis in understanding cancer lineages.
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Background: Neoantigen targeting therapies including personalized vaccines have shown promise in the treatment of cancers, particularly when used in combination with checkpoint blockade therapy. At least 100 clinical trials involving these therapies are underway globally. Accurate identification and prioritization of neoantigens is highly relevant to designing these trials, predicting treatment response, and understanding mechanisms of resistance.

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