A5015248299- Cancer Immunotherapy and Biomarkers
- Immunotherapy and Immune Responses
- CAR-T cell therapy research
- Immune Cell Function and Interaction
- Genetics, Bioinformatics, and Biomedical Research
- Science, Research, and Medicine
- Molecular Biology Techniques and Applications
- Biomedical and Engineering Education
- Biotechnology and Related Fields
- CRISPR and Genetic Engineering
- Glioma Diagnosis and Treatment
- Nutrition, Genetics, and Disease
- Immune cells in cancer
- Conferences and Exhibitions Management
- Cancer Genomics and Diagnostics
- Chemistry and Chemical Engineering
- Nanoplatforms for cancer theranostics
- Advanced Biosensing Techniques and Applications
- Animal Disease Management and Epidemiology
- T-cell and B-cell Immunology
- Scientific Computing and Data Management
- Cell Image Analysis Techniques
- Poverty, Education, and Child Welfare
- bioluminescence and chemiluminescence research
- Neuroblastoma Research and Treatments
University of Chicago
2012-2024
Massachusetts Institute of Technology
2019-2024
Akebia Therapeutics (United States)
2024
Koch Institute for Integrative Cancer Research At MIT
2017-2023
Allen Institute
2017-2023
IIT@MIT
2021
University of Illinois Chicago
2015-2017
The Nature Conservancy
1997-1998
<h3>Background</h3> Blockade of immune inhibitory pathways is emerging as an important therapeutic modality for the treatment cancer. Single agent treatments have partial anti-tumor activity in preclinical models and human cancer patients. Inasmuch tumor microenvironment shows evidence multiple mechanisms present concurrently, it has been reasoned that combination therapies may be required optimal effect. <h3>Methods</h3> To test this notion, we utilized permutations anti-CTLA-4 mAb,...
Although the presence of tumor-infiltrating lymphocytes (TILs) indicates an endogenous antitumor response, immune regulatory pathways can subvert effector phase and enable tumor escape. Negative include extrinsic suppression mechanisms, but also a T cell-intrinsic dysfunctional state. A more detailed study has been hampered by lack cell surface markers defining tumor-specific TILs, PD-1 alone is not sufficient. Recently, we identified transcription factor Egr2 as critical component in...
Abstract Subsets of human tumors are infiltrated with tumor antigen–specific CD8+ T cells [tumor-infiltrating lymphocytes (TILs)] despite progression. These TILs thought to be inactivated by the immunosuppressive microenvironment, through engagement inhibitory receptors such as CTLA-4 and PD-1. However, antigen-specific not functionally inert but undergoing activation in situ. Here, we show that actively proliferating, yet also undergo high rates apoptosis, leading a vicious cycle death...
A lung cancer–specific form of CD8 + T cell dysfunction is established during priming and contributes to ICB resistance.
The cellular source of positive signals that reinvigorate T cells within the tumor microenvironment (TME) for therapeutic efficacy programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade has not been clearly defined. We now show Batf3-lineage dendritic (DCs) are essential in this process. Flow cytometric analysis, gene-targeted mice, and blocking antibody studies revealed 4-1BBL is a major co-stimulatory signal provided by these DCs TME translates to CD8
Immune checkpoint blockade (ICB) enhances T cell responses against cancer, leading to long-term survival in a fraction of patients. CD8 + differentiation response chronic antigen stimulation is highly complex, and it remains unclear precisely which states at anatomic sites are critical for the ICB. We identified an intermediate-exhausted population white pulp spleen that underwent substantial expansion ICB gave rise tumor-infiltrating clonotypes. Increased systemic redirected this toward...
Engineered cytokine-based approaches for immunotherapy of cancer are poised to enter the clinic, with IL-12 being at forefront. However, little is known about potential mechanisms resistance cytokine therapies. We found that orthotopic murine lung tumors were resistant systemically delivered fused serum albumin (MSA, IL12-MSA) because low receptor (IL-12R) expression on tumor-reactive CD8+ T cells. IL2-MSA increased binding IL12-MSA by cells, and combined administration led enhanced cell...
Anticancer immunotherapies, such as immune checkpoint inhibitors, bispecific antibodies, and chimeric antigen receptor T cells, have improved outcomes for patients with a variety of malignancies. However, most either do not initially respond or exhibit durable responses due to primary adaptive/acquired resistance mechanisms the tumor microenvironment. These suppressive programs are myriad, different between ostensibly same cancer type, can harness multiple cell types reinforce their...
The recent successes of cancer immunotherapy, first and foremost checkpoint blockade therapy, illustrate the power immune system to control cancer. As number patients receiving this therapy is increasing, being resistant or establishing resistance toward immunotherapy also increasing. We, therefore, need further understand mechanisms mediate in order prevent overcome those mechanisms. Increasing evidence reported that alterations tumor cell-intrinsic signaling pathways, including activation...
<h3>Background</h3> Immune checkpoint blockade (ICB) provides durable clinical and survival benefits for a fraction of cancer patients.<sup>1–3</sup> ICB blocks interactions between inhibitory receptors expressed by exhausted CD8<sup>+</sup> T cells their ligands tumor or antigen-presenting cells, enhancing the functionality clonal expansion thereby improving overall anti-tumor immune response.<sup>4</sup> Recent studies have underscored remarkable heterogeneity within cell exhaustion...
<h3>Background</h3> IL-12 is a pleiotropic cytokine with potent T cell stimulatory ability that can induce tumor regression in pre-clinical models. Translation of has been hampered by high toxicity and lack efficacy. While many efforts have made to engineer be less toxic more effective, our understanding resistance limited due appropriate model systems. We identified IL-12-resistant lung cancer allows us probe mechanisms response resistance. <h3>Methods</h3> utilized the syngeneic,...