Jonathan Perera

Inflammatory cytokines induce new cancer dependencies

Collins K. Cheruiyot, Sarah Y. Kim, Juan Dubrot, Sarah Kate Lane-Reticker et autres

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Sialylated CD43 forms a glyco-immune barrier that restrains antileukemic immunity

Jooho Chung, Mounica Vallurupalli, Sarah Noel, Gail Schor et autres

Macrophages exert antitumorigenic activity through phagocytosis, but phagocytosis-enhancing therapeutics have not improved acute myeloid leukemia (AML) outcomes. To identify phagocytosis regulators, we performed CRISPR knockout screens in human AML cells cocultured with human macrophages. We found that the "don't eat me" signal …

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Lymphotoxin-driven cancer cell eradication by tumoricidal CD8 + TIL

Hongyan Xie, Aiping Jiang, Aonkon Dey, Joseph W. Dean et autres

Abstract Tumor-infiltrating lymphocyte (TIL) therapy is FDA-approved for patients with treatment-resistant advanced melanoma, but the TIL subpopulations critical for tumor eradication remains incompletely understood. Using patient-derived TIL-melanoma co-cultures, we identified and characterized a novel subset of CD8 + TIL, capable of class …

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371 Lymphotoxin-driven cancer cell eradication by tumoricidal CD8+ TIL

Hongyan Xie, Aiping Jiang, Aonkon Dey, Joseph W. Dean et autres

Background Tumor-infiltrating CD8 + T lymphocytes (TIL) are key determinants of response to immune checkpoint blockade (ICB) cancer immunotherapy and adoptive T cell therapy,1 2 but the identity of the subpopulations of TIL critical for tumor eradication remains incompletely understood.Methods To examine …

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In vivo CRISPR screening in head and neck cancer reveals Uchl5 as an immunotherapy target

Cong Fu, Robert Saddawi‐Konefka, Jordan M. Chinai, Sarah Y. Kim et autres

Recurrent/metastatic head and neck squamous cell carcinoma (HNSCC) is an aggressive malignancy with a significant unmet need for enhancing immunotherapy response given current modest efficacy. Here, we perform an in vivo CRISPR screen in an HNSCC mouse model to identify immune evasion …

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Sialylated CD43 is a glyco-immune checkpoint for macrophage phagocytosis

Jooho Chung, Mounica Vallurupalli, Gail Schor, YuhJong Liu et autres

Macrophages in the tumor microenvironment exert potent anti-tumorigenic activity through phagocytosis. Yet therapeutics that enhance macrophage phagocytosis have not improved outcomes in clinical trials for patients with acute myeloid leukemia (AML) or myelodysplastic syndrome (MDS). To systematically identify regulators of phagocytosis, we …

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Targeting the aminopeptidase ERAP enhances antitumor immunity by disrupting the NKG2A-HLA-E inhibitory checkpoint

Hsiao‐Wei Tsao, Seth W. Anderson, Kenneth J. Finn, Jonathan Perera et autres

The aminopeptidase, endoplasmic reticulum aminopeptidase 1 (ERAP1), trims peptides for loading into major histocompatibility complex class I (MHC class I), and loss of this activity has broad effects on the MHC class I peptidome. Here, we investigated the impact of targeting ERAP1 …

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Abstract 3968: Class I HLA-independent lysis of cancer cells by tumor-infiltrating CD8 T cells

Hongyan Xie, Aiping Jiang, Jonathan Perera, Aonkon Dey et autres

Abstract T cell-based therapies have transformed cancer treatment, although intrinsic or acquired resistance develops in nearly half of the patients. Tumor-infiltrating CD8+ T lymphocytes (TILs) are key determinants of anti-tumor immunity by secretion of cytotoxic granules, such as granzymes and perforin, and …

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399 Class I HLA-independent lysis of cancer cells by tumor-infiltrating CD8 T cells

Hongyan Xie, Aiping Jiang, Jonathan Perera, Moshe Sade-Feldman et autres

Background Cancer immunotherapy with immune checkpoint blockade (ICB) has transformed the treatment of melanoma, although treatment resistance is common and fatal. Tumor-infiltrating CD8+ T lymphocytes (TILs) are key determinants of ICB response, and strategies to enhance tumor cell sensitivity to TILs is …

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Emerging point‐of‐care autologous cellular therapy using adipose‐derived stromal vascular fraction for neurodegenerative diseases

Rawan Al‐kharboosh, Jonathan Perera, Alexandra R. Bechtle, Guojun Bu et autres

Neurodegenerative disorders are characterized by the gradual decline and irreversible loss of cognitive functions and CNS structures. As therapeutic recourse stagnates, neurodegenerative diseases will cost over a trillion dollars by 2050. A dearth of preventive and regenerative measures to hinder regression and …

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Neuronal CaMKK2 promotes immunosuppression and checkpoint blockade resistance in glioblastoma

William H. Tomaszewski, Jessica Waibl Polania, Molly A. Chakraborty, Jonathan Perera et autres

Abstract Glioblastoma (GBM) is notorious for its immunosuppressive tumor microenvironment (TME) and is refractory to immune checkpoint blockade (ICB). Here, we identify calmodulin-dependent kinase kinase 2 (CaMKK2) as a driver of ICB resistance. CaMKK2 is highly expressed in pro-tumor cells and is …

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Abstract 1378: CD8 T cell mediated killing of MHC class 1 negative tumors requires antigen presenting myeloid cells and interferon gamma

Emily Lerner, Vincent M. D’Anniballe, William H. Tomaszewski, Jonathan Perera et autres

Abstract Major Histocompatibility Complex (MHC) Class I downregulation is a well described mechanism of tumor immune escape, posing a challenge for T cell based immunotherapies including immune checkpoint blockade (ICB). Recent studies, however, have demonstrated mixed roles of MHC Class 1 and …

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