Graham Hogg

Program: Immunology

Current advisor: David G. DeNardo, PhD

Undergraduate university: Rice University, 2015

Enrollment year: 2016

Research summary
Harnessing Dendritic Cells as a Novel Therapy in Pancreatic Cancer

Checkpoint therapies have delivered unprecedented responses in malignancies such as melanoma and non-small-cell lung cancer. Unfortunately, checkpoint therapies are ineffective in Pancreatic Ductal Adenocarcinoma (PDAC). PDAC remains a devastating disease, with a 5-year-survival rate of less than 10% and new therapies are urgently needed. ;One possible explanation for the lack of checkpoint efficacy is that the pancreas is nearly devoid of conventional dendritic cells (cDCs). cDCs are highly specialized antigen presenting cells that can efficiently process cancer antigens and prime naïve T cells. Mounting evidence implicates cDCs as critical for tumor immune recognition. To overcome this mechanism of immune-evasion, I am investigating a novel combination immunotherapy in which cDCs are expanded with the cytokine Flt3L and licensed with a CD40 agonist antibody. Unexpectedly, the dual therapy results in a log fold increase in both intra-tumoral cDCs and T cells when compared with single arm Flt3L or CD40 alone. Additionally, we observe disease stabilization in our genetic mouse model of PDAC, which like the human disease is highly resistant to therapy. The canonical mechanism-of-action of either drug alone does not adequately predict the sum of their effects. Thus, I aim to elucidate the mechanisms through which the combination of Flt3L and CD40 drive anti-tumor immunity and disease control.

Graduate publications
Liu X, Hogg GD, Zuo C, Borcherding NC, Baer JM, Lander VE, Kang LI, Knolhoff BL, Ahmad F, Osterhout RE, Galkin AV, Bruey JM, Carter LL, Mpoy C, Vij KR, Fields RC, Schwarz JK, Park H, Gupta V, DeNardo DG. 2023 Context-dependent activation of STING-interferon signaling by CD11b agonists enhances anti-tumor immunity. Cancer Cell, 41(6):1073-1090.e12. PMCID: PMC10281762

Herzog BH, Baer JM, Borcherding N, Kingston NL, Belle JI, Knolhoff BL, Hogg GD, Ahmad F, Kang LI, Petrone J, Lin CY, Govindan R, DeNardo DG. 2023 Tumor-associated fibrosis impairs immune surveillance and response to immune checkpoint blockade in non-small cell lung cancer. Sci Transl Med, 15(699):eadh8005. PMCID:

Zuo C, Baer JM, Knolhoff BL, Belle JI, Liu X, Alarcon De La Lastra A, Fu C, Hogg GD, Kingston NL, Breden MA, Dodhiawala PB, Zhou DC, Lander VE, James CA, Ding L, Lim KH, Fields RC, Hawkins WG, Weber JD, Zhao G, DeNardo DG. 2023 Stromal and therapy-induced macrophage proliferation promotes PDAC progression and susceptibility to innate immunotherapy. J Exp Med, 220(6):e20212062. PMCID: PMC10072222

James CA, Baer JM, Zuo C, Panni UY, Knolhoff BL, Hogg GD, Kingston NL, Kang LI, Lander VE, Luo J, Tao Y, Watson MA, Aft R, Fields RC, Hawkins WG, DeNardo DG. 2023 Systemic Alterations in Type-2 Conventional Dendritic Cells Leads to Impaired Tumor Immunity in Pancreatic Cancer. Cancer Immunol Res, ():Online ahead of print. PMCID:

Selli ME, Landmann JH, Terekhova M, Lattin J, Heard A, Hsu YS, Chang TC, Chang J, Warrington J, Ha H, Kingston N, Hogg G, Slade M, Berrien-Elliott MM, Foster M, Kersting-Schadek S, Gruszczynska A, DeNardo D, Fehniger TA, Artyomov M, Singh N. 2023 Costimulatory domains direct distinct fates of CAR-driven T-cell dysfunction. Blood, 141(26):3153-3165. PMCID:

Lander VE, Belle JI, Kingston NL, Herndon JM, Hogg GD, Liu X, Kang LI, Knolhoff BL, Bogner SJ, Baer JM, Zuo C, Borcherding NC, Lander DP, Mpoy C, Scott J, Zahner M, Rogers BE, Schwarz JK, Kim H, DeNardo DG. 2022 Stromal reprogramming by FAK inhibition overcomes radiation resistance to allow for immune priming and response to checkpoint blockade. Cancer Discov, 12(12):2774-99. PMCID: PMC9722639

Peng H, James CA, Cullinan DR, Hogg GD, Mudd JL, Zuo C, Takchi R, Caldwell KE, Liu J, David DG, Fields RC, Gillanders WE, Goedegebuure SP, Hawkins WG. 2021 Neoadjuvant FOLFIRINOX therapy is associated with increased effector T cells and reduced suppressor cells in pancreatic cancer patients. Clin Cancer Res, (Sep. 30):clincanres.0998.2021. PMCID:

Liu X, Hogg GD, DeNardo DG. 2021 Rethinking immune checkpoint blockade: ‘Beyond the T cell’. J Immunother Cancer, 9(1):e001460

Hegde S, Krisnawan VE, Herzog BH, Zuo C, Breden MA, Knolhoff BL, Hogg GD, Tang JP, Baer JM, Mpoy C, Lee KB, Alexander KA, Rogers BE, Murphy KM, Hawkins WG, Fields RC, DeSelm CJ, Schwarz JK, DeNardo DG. 2020 Dendritic Cell Paucity Leads to Dysfunctional Immune Surveillance in Pancreatic Cancer. Cancer Cell, 37(3):289-307.e9. PMCID: PMC7181337

Panni RZ, Herndon JM, Zuo C, Hegde S, Hogg GD, Knolhoff BL, Breden MA, Li X, Krisnawan VE, Khan SQ, Schwarz JK, Rogers BE, Fields RC, Hawkins WG, Gupta V, DeNardo DG. 2019 Agonism of CD11b reprograms innate immunity to sensitize pancreatic cancer to immunotherapies. Sci Transl Med, 11(499):eaau9240. PMCID: PMC7197026