A5040684255- Immunotherapy and Immune Responses
- Cancer Immunotherapy and Biomarkers
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Angiogenesis and VEGF in Cancer
- RNA Interference and Gene Delivery
- Virus-based gene therapy research
- Immune cells in cancer
- T-cell and B-cell Immunology
- Cancer Genomics and Diagnostics
- Peptidase Inhibition and Analysis
Massachusetts Institute of Technology
2021-2025
Koch Institute for Integrative Cancer Research At MIT
2021-2023
Allen Institute
2021-2023
IIT@MIT
2021
Ragon Institute of MGH, MIT and Harvard
2021
A lung cancer–specific form of CD8 + T cell dysfunction is established during priming and contributes to ICB resistance.
Abstract Tumor cell–intrinsic signaling pathways can drastically affect the tumor immune microenvironment, promoting progression and resistance to immunotherapy by excluding immune-cell populations from tumor. Several have been reported modulate myeloid-cell T-cell infiltration creating “cold” tumors. However, clinical evidence suggests that cytotoxic T cells core also mediates evasion. Here, we find SOX2 in non-small cell lung cancer induces exclusion of promotes checkpoint blockade...
<div>Abstract<p>Tumor cell–intrinsic signaling pathways can drastically affect the tumor immune microenvironment, promoting progression and resistance to immunotherapy by excluding cell populations from tumor. Several have been reported modulate myeloid-cell T-cell infiltration, creating “cold” tumors. However, clinical evidence suggests that cytotoxic T cells core also mediates evasion. In this study, we find SOX2 in non–small lung cancer induces exclusion of promotes checkpoint...
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Abstract Tumor-intrinsic signaling pathways can drastically affect the tumor immune microenvironment (TME), promoting progression and resistance to immunotherapy by excluding cell populations from tumor. Several tumor-cell intrinsic have been reported myeloid infiltration downstream T infiltration. Clinical evidence suggests that exclusion of cytotoxic cells core likewise mediates resistance. Here, we find cell-intrinsic SOX2 expression induces promotes checkpoint blockade therapy. CD8 + was...
<h3>Background</h3> Although failure to respond checkpoint blockade immunotherapies is frequently associated with a lack of T-cell infiltration into the tumor, clinical data suggests that in patients lung cancer, T-cell-inflamed tumors can also be resistant therapy.<sup>1</sup> Work by us identified immunotherapy resistance cancer driven cancer-specific CD8<sup>+</sup> dysfunction, characterized reduced cytolytic capacity and established during priming mediastinal lymph nodes...
<h3>Background</h3> Pre-clinical models are crucial for better understanding and treating human diseases such as cancer. Autochthonous of lung cancer excellent tools to study tumor progression evolution. However, current approaches rely on intra-tracheal, viral delivery Cre recombinase initiate tumorigenesis by activating oncogenes deleting suppressor genes.<sup>1</sup> Two caveats this technique the lack cell-type specificity vectors resulting immunogenicity these vectors. We have...
<h3>Background</h3> Lack of response to checkpoint blockade immunotherapy has been linked a deficiency immune cell infiltration within the tumor microenvironment (TME). One demonstrated mechanism sufficient for non-T inflamed TME is cell-intrinsic activation β-catenin signaling pathway. Using genetically engineered mouse models (GEMMs), tumors constitutively expressing active lack robust endogenous T infiltrate and fail respond immunotherapies. In support these studies, human melanoma...
<h3>Background</h3> Immunotherapies such as checkpoint blockade therapy (CBT) can be an effective approach to treat patients with metastatic tumors. In non-small cell lung cancer (NSCLC), four major immune subsets have been described, (a) the CBT-sensitive T infiltration and PD-L1 expression, (b) desert that lacks CD8+ infiltration, (c) non-functional phenotype comprising cells yet no (d) excluded phenotype, characterized by effector surrounding tumor.<sup>1</sup>Patients a non-T...
Background Lung cancer is the leading cause of cancer-related death worldwide. 1 Immunotherapies such as checkpoint blockade therapy (CBT) can be an effective approach to treat patients with metastatic tumors. However, only a fraction responsive CBT treatments. 2 Patients non-T cell-infiltrated tumor microenvironment correlate poor response and T cell infiltration influenced by cell-intrinsic signaling pathways. 3 4 Therefore, understanding mechanisms affecting anti-tumor immune will aid us...
<h3>Background</h3> Although failure to respond checkpoint blockade immunotherapies (CBT) is frequently associated with a lack of T cell infiltration into the tumor, emerging clinical data suggests that specifically in patients lung cancer, cell-inflamed tumors can also be resistant therapy.<sup>1</sup> Recent work by our group identified immunotherapy resistance pre-clinical mouse model cancer driven cancer-specific CD8<sup>+</sup> dysfunctional program (T<sub>Ldys</sub>), characterized...