Thomas F Gajewski
University of Chicago
H-index: 113
North America-United States
Description
Thomas F Gajewski, With an exceptional h-index of 113 and a recent h-index of 74 (since 2020), a distinguished researcher at University of Chicago, specializes in the field of cancer, immunology.
His recent articles reflect a diverse array of research interests and contributions to the field:
Genetic elimination of β-catenin using a doxycycline-regulated GEM model fails to restore checkpoint blockade efficacy due to persistent M2-like macrophages
Batf3+ DCs and the 4-1BB/4-1BBL axis are required at the effector phase in the tumor microenvironment for PD-1/PD-L1 blockade efficacy
Neutralizing GDF-15 can overcome anti-PD-(L) 1 resistance in late-stage cancer
Beta-catenin inhibitors in cancer immunotherapy
Synergistic innate immune activation and anti-tumor immunity through combined STING and TLR4 stimulation
Methods and compositions related to t-cell activity
Decr2 regulates tumor cell ferroptosis and immunotherapy efficacy
Targeting murine or human KLRG1 exerts potent anti-tumor efficacy involving both CD8T cells and NK cells
Professor Information
University | University of Chicago |
---|---|
Position | Professor |
Citations(all) | 67072 |
Citations(since 2020) | 36256 |
Cited By | 46067 |
hIndex(all) | 113 |
hIndex(since 2020) | 74 |
i10Index(all) | 325 |
i10Index(since 2020) | 197 |
University Profile Page | University of Chicago |
Research & Interests List
cancer
immunology
Top articles of Thomas F Gajewski
Genetic elimination of β-catenin using a doxycycline-regulated GEM model fails to restore checkpoint blockade efficacy due to persistent M2-like macrophages
Response to checkpoint blockade immunotherapy (CBI) is not universal, partly due to a wide variation in baseline immune cell infiltration in the tumor microenvironment (TME). One mechanism contributing to this variability is tumor cell-intrinsic activation of the β-catenin signaling pathway, which has previously been shown to result in a non-T cell-inflamed TME. Constitutive β-catenin signaling resulted in reduced Batf3-lineage dendritic cell (cDC1) recruitment, leading to reduced T cell activation and infiltration and loss of anti-CTLA-4+anti-PD-L1 therapeutic efficacy. Efforts to target the Wnt/β-catenin pathway to enhance immune responses in β-catenin-active tumors have seen limited success. A genetic experiment eliminating β-catenin expression after establishment of a non-T cell-inflamed TME might illustrate the maximal biologic effect that could be expected with blockade of the pathway. We developed a …
Authors
Alexandra Cabanov,Ruxandra Tonea,Jason Shapiro,Anna Martinez,Yuanyuan Zha,Thomas F Gajewski
Journal
Cancer Research
Published Date
2024/3/22
Batf3+ DCs and the 4-1BB/4-1BBL axis are required at the effector phase in the tumor microenvironment for PD-1/PD-L1 blockade efficacy
The cellular source of positive signals that reinvigorate T cells within the tumor microenvironment (TME) for the therapeutic efficacy of programmed death-1 (PD-1)/programmed death-ligand 1 (PD-L1) blockade has not been clearly defined. We now show that Batf3-lineage dendritic cells (DCs) are essential in this process. Flow cytometric analysis, gene-targeted mice, and blocking antibody studies revealed that 4-1BBL is a major positive co-stimulatory signal provided by these DCs within the TME that translates to CD8+ T cell functional reinvigoration and tumor regression. Immunofluorescence and spatial transcriptomics on human tumor samples revealed clustering of Batf3+ DCs and CD8+ T cells, which correlates with anti-PD-1 efficacy. In addition, proximity to Batf3+ DCs within the TME is associated with CD8+ T cell transcriptional states linked to anti-PD-1 response. Our results demonstrate that Batf3+ DCs …
Authors
Andrea Ziblat,Brendan L Horton,Emily F Higgs,Ken Hatogai,Anna Martinez,Jason W Shapiro,Danny EC Kim,YuanYuan Zha,Randy F Sweis,Thomas F Gajewski
Journal
Cell Reports
Published Date
2024/5/28
Neutralizing GDF-15 can overcome anti-PD-(L) 1 resistance in late-stage cancer
Cancer immunotherapies with antibodies blocking immune checkpoint molecules are active treatments across multiple cancer entities and have markedly improved cancer treatment. Yet, response rates are still limited, and tumor progression commonly occurs. Soluble and cell-bound factors in the tumor microenvironment negatively impact on cancer immunity. Recently, Growth and Differentiation-factor 15 (GDF-15), a cytokine that is abundantly produced by many cancer types, was shown to interfere with anti-tumor immune response. In preclinical cancer models, GDF-15 blockade synergistically enhanced the efficacy of anti-PD-1 mediated checkpoint inhibition. In a first-in-human phase 1/2a study (GDFATHER-1/2a trial, NCT04725474), patients with advanced cancers refractory to anti-PD-(L) 1 therapy were treated with the neutralizing anti-GDF-15 antibody visugromab (CTL-002) in combination with the anti-PD-1 antibody nivolumab. Durable responses were achieved namely in patients with non-squamous non-small cell lung cancer and urothelial cancer, two cancer entities identified as frequently GDF-15 immunosuppressed in an in-silico 11,000 tumor TCGA data base screening. Increased tumor infiltrates, proliferation and Granzyme-B expression in cytotoxic T-cells were observed in response to therapy. Neutralizing GDF-15 holds promise in overcoming resistance to immune checkpoint inhibition in cancer.
Authors
Ignacio Melero,María de Miguel Luken,Guillermo de Velasco,Elena Garralda,Juan Martin Liberal,Markus Joerger,Guzman Alonso,Maria-Elizabeth Goebeler,Martin Schuler,David König,Reinhard Dummer,Mara Reig,Maria Rodriguez-Ruiz,Emiliano Calvo,Jorge Esteban-Villarrubia,Arjun Oberoi,Paula Sàbat,Juan José Soto-Castillo,Kira-Lee Koster,Omar Saavedra,Cyrus Sayehli,Tanja Gromke,Heinz Läubli,Egle Ramelyte,Marta Fortuny,Ana Landa-Magdalena,Irene Moreno,Javier Torres-Jiménez,Alberto Hernando-Calvo,Dagmar Hess,Fabricio Racca,Heike Richly,Andreas Schmitt,Corinne Eggenschwiler,Marco Sanduzzi-Zamparelli,Anna Vilalta-Lacarra,Zlatko Trajanoski,Hubert Hackl,Falk Gogolla,Florestan Koll,Peter Wild,Felix Kyoung-Hwan Chun,Henning Reis,Peter Lloyd,Matthias Machacek,Thomas F Gajewski,Wolf FRIDMAN,Alexander Eggermont,Ralf Bargou,Sandra Schöniger,Josef Rüschoff,Anastasiia Tereshchenko,Carina Zink,Antonio da Silva,Felix Lichtenegger,Julia Akdemir,Manfred Rüdiger,Phil L’Huillier,Aradhana Dutta,Markus Haake,Alexandra Auckenthaler,Ana Gjorgjioska,Frank Hermann,Bernhard Rössler,Mara Liebig,Christine Schuberth-Wagner,Marlene Auer,Jörg Wischhusen,Petra Fettes,Kathrin Klar,Eugen Leo
Published Date
2024/3/7
Beta-catenin inhibitors in cancer immunotherapy
Provided herein are compositions and methods for the treatment of cancer by inhibition off-catenin or a f-catenin pathway. In particular, inhibitors of f-catenin and/or the Wnt/f-catenin signaling pathway are employed prevent or reverse evasion of immune response or immunotherapy by
Published Date
2024/4/2
Synergistic innate immune activation and anti-tumor immunity through combined STING and TLR4 stimulation
Previous work has shown that innate immune sensing of tumors involves the host STING pathway, which leads to IFN-B production, dendritic cell (DC) activation, and T cell priming against tumor antigens. This observation has led to the development of STING agonists as a potential cancer therapeutic. However, despite promising results in mouse studies using transplantable tumor models, clinical testing of STING agonists has shown activity in only a minority of patients. Thus, further study of innate immune pathways in anti-tumor immunity is paramount. Innate immune activation in response to a pathogen rarely occurs through stimulation of only one signaling pathway, and activating multiple innate immune pathways similar to a natural infection is one possible strategy to improve the efficacy of STING agonists. To test this, we performed experiments with the STING agonist DMXAA alone or in combination with several TLR agonists. We found that LPS + DMXAA induced significantly greater IFN-B transcription than the sum of either agonist alone. To explain this synergy, we assayed each step of STING pathway signaling. LPS did not increase STING protein aggregation, IRF3 phosphorylation, or IRF3 nuclear translocation beyond what occurred with DMXAA alone. However, since the IFN-B promoter also includes NF-kB binding sites, we additionally examined the NF-kB pathway. In fact, LPS increased the phosphorylation and nuclear translocation of the NF-kB subunit p65, and NF-kB signaling was required for the observed synergy. Intratumoral injection of suboptimal doses of LPS + DMXAA resulted in significantly improved tumor control of B16 …
Authors
Emily F Higgs,Thomas F Gajewski
Journal
bioRxiv
Published Date
2024
Methods and compositions related to t-cell activity
Embodiments concern methods and composition related to anergic T-cells in patients, such as cancer patients.
Published Date
2023/10/31
Decr2 regulates tumor cell ferroptosis and immunotherapy efficacy
Checkpoint blockade therapies have transformed the landscape of cancer care. Durable clinical responses have been observed in a subset of patients. However, many patients do not respond, and understanding the mechanisms that determine tumor resistant to checkpoint blockade drugs could potentially benefit more patients. Ferroptosis is a relatively newly described form of regulated cell death distinct from apoptosis and necroptosis. Recently, T cell-promoted tumor ferroptosis was shown to be an anti-tumor mechanism and targeting this pathway could be a potential therapeutic approach. To identify genes critical to immunotherapy resistance, B16.SIY cells were transduced with a genome-scale gRNA lentivirus to generate loss of function mutants. In vitro-primed CD8+ T cells isolated from 2C/Rag2-/- TCR transgenic mice specific for the SIY antigen were co-cultured with transduced B16.SIY tumor cells …
Authors
Shuyin Li,Jason Shapiro,Hardik Shah,Emily F Higgs,Lishi Xie,Yuanyuan Zha,Jonathan Trujillo,Alexandra Cabanov,Tyler A Jones,Blake Flood,Ken Hatogai,Justin Kline,Thomas F Gajewski
Journal
Cancer Research
Published Date
2024/3/22
Targeting murine or human KLRG1 exerts potent anti-tumor efficacy involving both CD8T cells and NK cells
Clinical response to anti-PD-1 immunotherapy is correlated with patients who have a T cell-inflamed tumor microenvironment. Some patients with immune cell infiltration fail to respond, and some patients experiencing an initial clinical response develop acquired resistance. It is likely that additional immune-regulatory pathways need to be targeted to expand the efficacy of immunotherapies. To identify a broader array of therapeutic relevant immunotherapy molecules in T cell-inflamed tumors, our lab utilized gene expression profiling to characterize tumor antigen-specific dysfunctional CD8+ T cells in the tumor microenvironment. One molecule that was found to be overexpressed on these CD8+ T cells was C-type lectin inhibitory receptor, KLRG1. KLRG1 is an ITIM domain-containing receptor mostly explored on NK cells, and the known ligands are N- and E- cadherins which are broadly expressed in solid cancers …
Authors
Tyler A Jones,Stephen Sinicrope,Kei Yasuda,Jan Pinkas,Thomas F Gajewski
Journal
Cancer Research
Published Date
2024/3/22
Professor FAQs
What is Thomas F Gajewski's h-index at University of Chicago?
The h-index of Thomas F Gajewski has been 74 since 2020 and 113 in total.
What are Thomas F Gajewski's top articles?
The articles with the titles of
Genetic elimination of β-catenin using a doxycycline-regulated GEM model fails to restore checkpoint blockade efficacy due to persistent M2-like macrophages
Batf3+ DCs and the 4-1BB/4-1BBL axis are required at the effector phase in the tumor microenvironment for PD-1/PD-L1 blockade efficacy
Neutralizing GDF-15 can overcome anti-PD-(L) 1 resistance in late-stage cancer
Beta-catenin inhibitors in cancer immunotherapy
Synergistic innate immune activation and anti-tumor immunity through combined STING and TLR4 stimulation
Methods and compositions related to t-cell activity
Decr2 regulates tumor cell ferroptosis and immunotherapy efficacy
Targeting murine or human KLRG1 exerts potent anti-tumor efficacy involving both CD8T cells and NK cells
...
are the top articles of Thomas F Gajewski at University of Chicago.
What are Thomas F Gajewski's research interests?
The research interests of Thomas F Gajewski are: cancer, immunology
What is Thomas F Gajewski's total number of citations?
Thomas F Gajewski has 67,072 citations in total.