Kai Stewart

Follicular Lymphoma Transformation is Characterized by Cytokine-associated Remodeling of Stromal and Macrophage Compartments

Nicholas J. Haradhvala, Stephanie Pei Tung Yiu, Laura Beckmann, Sam Sadigh et autres

Across cancer, one of the most frequent examples of histologic transformation is the evolution of follicular lymphoma (FL) to an aggressive large cell lymphoma. Despite recent progress, understanding of the molecular and cellular underpinnings of transformation remains incomplete. Here, we dissect the …

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Abstract PR001: Cytokine-linked stromal remodeling in transformed follicular lymphoma impacts macrophage function and can be detected non-invasively

Laura Beckmann, Nicholas J. Haradhvala, Stephanie Pei Tung Yiu, Sam Sadigh et autres

Introduction: Despite transformation of indolent follicular lymphoma (FL) into aggressive lymphoma (transformed FL, tFL) remaining the main cause of disease-related mortality, the underlying mechanisms of transformation remain incompletely understood. With recent evidence suggesting that non-malignant populations in the microenvironment contribute to the …

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NEO-STIM advances personalized neoantigen-specific adoptive T cell therapy

Divya Lenkala, Jessica Kohler, Brian McCarthy, Michael S. Nelson et autres

Abstract Neoantigen-based adoptive T cell therapies (ACTs) represent a promising avenue in cancer immunotherapy due to their exquisite tumor specificity. The first cell-based immunotherapy for a solid tumor, comprising tumor-infiltrating lymphocytes, recently received FDA approval. Building on this, we designed a distinct …

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Abstract P3-04-06: Genomic and transcriptomic profiling of BRCA mutation carrier tissues reveals the landscape of early pathogenesis of BRCA1/2-associated breast cancer

Zuen Ren, Siang‐Boon Koh, Kai Stewart, Nick Haradhvala et autres

Abstract Women who harbor germline heterozygous mutations of BRCA1 or BRCA2 have a high risk of breast cancer. Our previous study showed that patient-derived, ostensibly normal BRCA2mut/+ luminal progenitor (LP) cells are more prone to exhibit sub-chromosomal copy number variations and associated …

Abstract 767: Genomics and transcriptomics profiling of BRCA mutation carriers revealed the landscape of early pathogenesis of BRCA1/2-associated breast cancer

Zuen Ren, Po‐Han Lin, Siang‐Boon Koh, Kai Stewart et autres

Abstract Women who harbor germline heterozygous mutations of BRCA1 or BRCA2 have a high risk of breast cancer. Our previous study showed that patient-derived, ostensibly normal BRCA2mut/+ luminal progenitor (LP) cells are more prone to exhibit sub-chromosomal copy number variations and associated …

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Loss of IFNgR1 signaling glioblastoma drives resistance to CAR T cell binding avidity and cytotoxicity due to lower downstream expression of ICAM-1

Rebecca Larson, Michael Kann, Stefanie R. Bailey, Nicholas J. Haradhvala et autres

Abstract Though CAR T cell therapy has had success treating hematologic malignancies, these treatments have shown only modest efficacy in solid tumors. Little is known about the necessary molecular components required for CAR T cell cytotoxicity, especially in the context of solid …

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CAR T cell killing requires the IFNγR pathway in solid but not liquid tumours

Rebecca C. Larson, Michael C. Kann, Stefanie R. Bailey, Nicholas J. Haradhvala et autres

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221 CRISPR screen identifies loss of IFNγR signaling and downstream adhesion as a resistance mechanism to CAR T-cell cytotoxicity in solid but not liquid tumors

Rebecca C. Larson, Michael C. Kann, Stefanie R. Bailey, Nicholas J. Haradhvala et autres

Background Chimeric Antigen Receptor (CAR) therapy has had a transformative impact on the treatment of hematologic malignancies1–6 but success in solid tumors remains elusive. We hypothesized solid tumors have cell-intrinsic resistance mechanisms to CAR T-cell cytotoxicity. Methods To systematically identify resistance pathways, …

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