Curtis J. Wray
Current Organizations / Institutes
The organizations/institutes from the scholar's latest article
Previous Organizations / Institutes
The organizations / institutes from the scholar's other articles in the past ten years
Curtis J. Wray has a total of 258 co-authors. Here are the top co-authors by number of shared publications:
- Nirav C. Thosani
Department of Internal Medicine, The University of Texas Health Science Center at Houston, Houston, TX
56 shared publications - Jennifer M. Bailey-Lundberg
University of Nebraska Medical Center
53 shared publications - Kyle Lauren Poulsen
Department of Anesthesiology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas
51 shared publications - Lincoln N. Strickland
Department of Pathology, Microbiology and Immunology, The University of Nebraska Medical Center, Omaha, NE
51 shared publications - Baylee J. O'BRien
Department of Anesthesiology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas
50 shared publications - Erika Y. Faraoni
Department of Anesthesiology, McGovern Medical School, The University of Texas Health Science Center at Houston, Houston, Texas
50 shared publications
Latest Publications
- Open Access
Combination Immunotherapy Enhances Serial Radiofrequency Ablation Induced Systemic Antitumor Immunity in Pancreatic Cancer
Thermal ablation is increasingly used for local control of pancreatic ductal adenocarcinoma (PDAC), but its capacity to induce systemic antitumor immunity and the mechanisms limiting this response remain incompletely defined. Using a bilateral LSL-Kras G12D/+; LSL-Trp53 R172H/+ ; Pdx1-Cre (KPC) flank tumor model, we show serial radiofrequency ablation (RFA) enhances local tumor control and induces a robust abscopal response. This effect was associated with increased activation of CD8⁺ T cells and natural killer cells, and was abrogated by CD8⁺ T cell depletion. Single-cell RNA sequencing revealed expansion of cytotoxic immune programs alongside induction of a CSF1R-driven myeloid response consistent with adaptive immune resistance. Although combinatorial blockade of PD-L1 and CD73 augmented systemic antitumor responses, and the addition of CSF1R inhibition in this context further enhanced both local and distant tumor control. These findings identify a CSF1R-dependent myeloid resistance program which constrains ablation-induced systemic immunity and demonstrate that rational combination immunotherapy can potentiate the systemic efficacy of tumor ablation in PDAC. STATEMENT OF TRANSLATIONAL RELEVANCE: Radiofrequency ablation is a local thermal therapy that induces tumor destruction and modulation of the tumor microenvironment used for treatment of many solid tumors, including pancreatic cancer. Serial thermal ablations induce a CD8+ T cells and NK cell antitumor immunological response; however, Nt5e (CD73) is increased in tumor cells, PD-1 is increased in CD8+ T cells, and serial ablations increase a CSF1R+ macrophage cluster in ablated tumors. Combinational targeting of CD73, PD-L1, and CSF1R alleviates CSF1R-dependent therapeutic resistance and enhances local and systemic tumor control. This study identifies targetable countervailing mechanisms to local ablation therapy and provides a rationale for combinatorial strategies integrating serial tumor ablation with systemic immunomodulatory agents. Future prospective studies should evaluate the influence of timing, dosage, and sequence of ablation on immune priming to improve clinical interventions in pancreatic cancer.
Open AccessCombination Immunotherapy Enhances Serial Radiofrequency Ablation Induced Systemic Antitumor Immunity in Pancreatic Cancer
Thermal ablation is increasingly used for local control of pancreatic ductal adenocarcinoma (PDAC), but its capacity to induce systemic antitumor immunity and the mechanisms limiting this response remain incompletely defined. Using a bilateral LSL-Kras G12D/+; LSL-Trp53 R172H/+ ; Pdx1-Cre (KPC) flank tumor model, we show serial radiofrequency ablation (RFA) enhances local tumor control and induces a robust abscopal response. This effect was associated with increased activation of CD8⁺ T cells and natural killer cells, and was abrogated by CD8⁺ T cell depletion. Single-cell RNA sequencing revealed expansion of cytotoxic immune programs alongside induction of a CSF1R-driven myeloid response consistent with adaptive immune resistance. Although combinatorial blockade of PD-L1 and CD73 augmented systemic antitumor responses, and the addition of CSF1R inhibition in this context further enhanced both local and distant tumor control. These findings identify a CSF1R-dependent myeloid resistance program which constrains ablation-induced systemic immunity and demonstrate that rational combination immunotherapy can potentiate the systemic efficacy of tumor ablation in PDAC. STATEMENT OF TRANSLATIONAL RELEVANCE: Radiofrequency ablation is a local thermal therapy that induces tumor destruction and modulation of the tumor microenvironment used for treatment of many solid tumors, including pancreatic cancer. Serial thermal ablations induce a CD8+ T cells and NK cell antitumor immunological response; however, Nt5e (CD73) is increased in tumor cells, PD-1 is increased in CD8+ T cells, and serial ablations increase a CSF1R+ macrophage cluster in ablated tumors. Combinational targeting of CD73, PD-L1, and CSF1R alleviates CSF1R-dependent therapeutic resistance and enhances local and systemic tumor control. This study identifies targetable countervailing mechanisms to local ablation therapy and provides a rationale for combinatorial strategies integrating serial tumor ablation with systemic immunomodulatory agents. Future prospective studies should evaluate the influence of timing, dosage, and sequence of ablation on immune priming to improve clinical interventions in pancreatic cancer.