Jonathan Chee
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Age-dependent tumor-immune interactions underlie immunotherapy response in pediatric cancer Open
SUMMARY Pediatric cancers originate in rapidly growing tissues within the context of a developing host. However, the interactions between cancer cells and the developing immune system are incompletely understood. Here, we established a sui…
View article: Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy
Coupling of response biomarkers between tumor and peripheral blood in patients undergoing chemoimmunotherapy Open
Platinum-based chemotherapy in combination with anti-PD-L1 antibodies has shown promising results in mesothelioma. However, the immunological mechanisms underlying its efficacy are not well understood and there are no predictive biomarkers…
View article: Anti-metabolite chemotherapy increases LAG-3 expressing tumor-infiltrating lymphocytes which can be targeted by combination immune checkpoint blockade
Anti-metabolite chemotherapy increases LAG-3 expressing tumor-infiltrating lymphocytes which can be targeted by combination immune checkpoint blockade Open
Background Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA-4), programmed cell death protein/ligand 1 (PD-1/PD-L1) are approved for treatment of multiple cancer types. Chemotherapy is often administ…
View article: Immune checkpoint therapy responders display early clonal expansion of tumor infiltrating lymphocytes
Immune checkpoint therapy responders display early clonal expansion of tumor infiltrating lymphocytes Open
Immune checkpoint therapy (ICT) causes durable tumour responses in a subgroup of patients, but it is not well known how T cell receptor beta (TCRβ) repertoire dynamics contribute to the therapeutic response. Using murine models that exclud…
View article: Early clonal expansion of tumor-infiltrating lymphocytes predicts response to immune checkpoint therapy
Early clonal expansion of tumor-infiltrating lymphocytes predicts response to immune checkpoint therapy Open
Immune checkpoint therapy (ICT) causes durable tumor responses in a subgroup of patients. Profiling T cell receptor beta (TCRβ) repertoire structure in ICT responders and non-responders provides mechanistic insight into what constitutes an…
Comprehensive Testing of Chemotherapy and Immune Checkpoint Blockade in Preclinical Cancer Models Identifies Additive Combinations Open
Antibodies that target immune checkpoints such as cytotoxic T lymphocyte antigen 4 (CTLA‐4) and the programmed cell death protein 1/ligand 1 (PD-1/PD-L1) are now a treatment option for multiple cancer types. However, as a monotherapy, obje…
Interferons limit autoantigen-specific CD8+ T-cell expansion in the non-obese diabetic mouse Open
Interferon gamma (IFNγ) is a proinflammatory cytokine implicated in autoimmune diseases. However, deficiency or neutralization of IFNγ is ineffective in reducing disease. We characterize islet antigen-specific T cells in non-obese diabetic…
Diabetes induced by checkpoint inhibition in nonobese diabetic mice can be prevented or reversed by a <span>JAK1</span>/<span>JAK2</span> inhibitor Open
Objectives Immune checkpoint inhibitors have achieved clinical success in cancer treatment, but this treatment causes immune‐related adverse events, including type 1 diabetes (T1D). Our aim was to test whether a JAK1/JAK2 inhibitor, effect…
View article: Dynamic changes in the T cell receptor repertoire during treatment with radiotherapy combined with an immune checkpoint inhibitor
Dynamic changes in the T cell receptor repertoire during treatment with radiotherapy combined with an immune checkpoint inhibitor Open
Previous studies have indicated a synergistic effect between radiotherapy and immunotherapy. A better understanding of how this combination affects the immune system can help to clarify its role in the treatment of metastatic cancer. We pe…
Characterization of neoantigen-specific T cells in cancer resistant to immune checkpoint therapies Open
Significance Strongly implicated in effective antitumor immune responses, tumor mutation–derived antigens, or neoantigens, are one of the main targets for cancer vaccines despite uncertainty of the efficacy of this approach. Using a high-t…
Malignant Pleural Effusions—A Window Into Local Anti-Tumor T Cell Immunity? Open
The success of immunotherapy that targets inhibitory T cell receptors for the treatment of multiple cancers has seen the anti-tumor immune response re-emerge as a promising biomarker of response to therapy. Longitudinal characterization of…
Tumour draining lymph node-generated CD8 T cells play a role in controlling lung metastases after a primary tumour is removed but not when adjuvant immunotherapy is used Open
Surgical resection of cancer remains the frontline therapy for millions of patients annually, but post-operative recurrence is common, with a relapse rate of around 45% for non-small cell lung cancer. The tumour draining lymph nodes (dLN) …
Tolerance to Proinsulin-1 Reduces Autoimmune Diabetes in NOD Mice Open
T-cell responses to insulin and its precursor proinsulin are central to islet autoimmunity in humans and non-obese diabetic (NOD) mice that spontaneously develop autoimmune diabetes. Mice have two proinsulin genes proinsulin -1 and 2 that …
Tumor Infiltrating Effector Memory Antigen-Specific CD8+ T Cells Predict Response to Immune Checkpoint Therapy Open
Immune checkpoint therapy (ICT) results in durable responses in individuals with some cancers, but not all patients respond to treatment. ICT improves CD8+ cytotoxic T lymphocyte (CTL) function, but changes in tumor antigen-specific CTLs p…
Characteristics of TCR Repertoire Associated With Successful Immune Checkpoint Therapy Responses Open
Immunotherapies have revolutionized cancer treatment. In particular, immune checkpoint therapy (ICT) leads to durable responses in some patients with some cancers. However, the majority of treated patients do not respond. Understanding imm…
Pre-treatment tumor neo-antigen responses in draining lymph nodes are infrequent but predict checkpoint blockade therapy outcome Open
Immune checkpoint blockade (ICPB) is a powerfully effective cancer therapy in some patients. Tumor neo-antigens are likely main targets for attack but it is not clear which and how many tumor mutations in individual cancers are actually an…
Impaired T cell proliferation by<i>ex vivo</i>BET-inhibition impedes adoptive immunotherapy in a murine melanoma model Open
Activation of naïve CD8+ T cells stimulates proliferation and differentiation into cytotoxic T-lymphocytes (CTLs). Adoptive T Cell Therapy (ACT) involves multiple rounds of ex vivo activation to generate enough CTLs for reinfusion into pat…
Acquired resistance during adoptive cell therapy by transcriptional silencing of immunogenic antigens Open
Immunotherapies such as adoptive cell therapy (ACT) are promising treatments for solid cancers. However, relapsing disease remains a problem and the molecular mechanisms underlying resistance are poorly defined. We postulated that the dere…
Combination immune checkpoint blockade as an effective therapy for mesothelioma Open
Mesothelioma is an aggressive asbestos induced cancer with extremely poor prognosis and limited treatment options. Immune checkpoint blockade (ICPB) has demonstrated effective therapy in melanoma and is now being applied to other cancers, …