Martin Cannon, PhD
University of Arkansas for Medical Sciences
College of Medicine
Microbiology & Immunology
Cancer Research Interest
- Disease Site Focus: Gynecology
- Research Focus Area: Treatment
- Type of Research: Clinical
- Research Interest Statement: Our laboratory at UAMS has a strong translational focus, with the goal of developing new treatments based on dendritic cell (DC) vaccination for gynecological malignancies. Recent clinical observations have shown that Th17 infiltration is associated with markedly improved overall survival. In partnership with the Mayo Clinic, we have recently completed a Phase I clinical trial of FR-targeted Th17-inducing DC vaccination in stage IIIC/IV ovarian cancer patients following surgery and chemotherapy. Th17-inducing DC vaccination induces consistent Th1/Th17 responses and antibody responses, and incurs minimal toxicity. Of 18 evaluable patients, 39% remain recurrence-free beyond 4 years post-enrollment. Although the clinical results are encouraging, one of the major barriers to clinical success of immunotherapy resides with immune suppression in the tumor microenvironment. Our current research explores the hypothesis that inhibition of homologous recombination and/or the replication stress response triggers an inflammatory response in the ovarian tumor microenvironment and alleviates myeloid cell-associated immune suppression, thereby boosting therapeutic responses to Th17-DC vaccination. Recent studies have shown that PARP inhibitors can activate innate and adaptive immune responses in ovarian cancer through the cGAS-STING pathway, thus providing a link between DNA damage, inflammatory responses and antitumor immunity. We have further shown that STING activation can reverse myeloid cell immune suppression of ovarian tumor antigen-specific T cell responses. These observations present a compelling case for the combination of PARP inhibitors and Th17-DC vaccination.
- Email Address: CANNONMARTIN@UAMS.EDU
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- NIH/Nat. Inst. of Allergy & Infectious Diseases – 1U01AI170039“Platelets in radiation-induced immune dysregulatio”Principal Investigator07/25/22 – 05/31/27
- NIH/Nat. Inst. of General Medical Sciences – 1P30GM145393“COBRE - Phase III Center for Microbial Pathogenesi”Co-Investigator05/05/22 – 04/30/27
- NIH/Nat. Inst. of General Medical Sciences – 1P30GM145393“COBRE - Phase III”Co-Investigator05/05/22 – 04/30/27
- NIH/Nat. Cancer Institute – 1R01CA245083“Improvement of cellular immunotherapy during dysbi”Co-Investigator09/15/21 – 08/31/26
- National Aeronautics & Space Administration – 80NSSC21M0323“Preventing immune system dysregulation during deep”Co-Investigator08/15/21 – 08/14/24
- US Department of Defense – W81XWH2110460“Proteogenomic analysis of responders versus nonres”Principal Investigator07/01/21 – 06/30/23
- Ovarian Cancer Research Fund Alliance – 813467“Understanding and targeting myeloid populations”Principal Investigator01/01/21 – 12/31/23
- Congressionally Directed Medical Research Programs – W81XWH2010642“Enhancement of Th17-Inducing DC Vaccination for Ovarian Cancer Through PARPi-Mediated Activation of Innate Immunity in the Tumor Microenvironment”Principal Investigator08/01/20 – 07/31/23
- Nagalo BM, Zhou Y, Loeuillard EJ, [et al., including Cannon MJ]. Characterization of Morreton virus as an oncolytic virotherapy platform for liver cancers. Hepatology (Baltimore, Md.). 2022. PMID: 36052732.
- Conrad SJ, Raza T, Peterson EA, [et al., including Cannon M]. Myxoma virus lacking the host range determinant M062 stimulates cGAS-dependent type 1 interferon response and unique transcriptomic changes in human monocytes/macrophages. PLoS pathogens. 2022 18(9):e1010316. PMID: 36103568. PMCID: PMC9473615.
- Zhang Y, Gabere M, Taylor MA, [et al., including Cannon MJ]. Repurposing live attenuated trivalent MMR vaccine as cost-effective cancer immunotherapy. Frontiers in oncology. 2022 12:1042250. PMID: 36457491. PMCID: PMC9706410.
- Block MS, Dietz AB, Gustafson MP, [et al., including Cannon MJ]. Th17-inducing autologous dendritic cell vaccination promotes antigen-specific cellular and humoral immunity in ovarian cancer patients. Nature communications. 2020 11(1):5173. PMID: 33057068. PMCID: PMC7560895.
- Jenkins SV, Robeson MS 2nd, Griffin RJ, [et al., including Cannon MJ]. Gastrointestinal Tract Dysbiosis Enhances Distal Tumor Progression through Suppression of Leukocyte Trafficking. Cancer research. 2019 79(23):5999-6009. PMID: 31591154. PMCID: PMC6891208.
- Cannon MJ, Block MS, Morehead LC, Knutson KL. The evolving clinical landscape for dendritic cell vaccines and cancer immunotherapy. Immunotherapy. 2019 11(2):75-79. PMID: 30730268.
- Morehead LC, Cannon MJ. Further clinical advancement of dendritic cell vaccination against ovarian cancer. Annals of research hospitals. 2018 2. PMID: 30345421. PMCID: PMC6192055.
- Ou Y, Cannon MJ, Nakagawa M. Regulatory T Cells in Gynecologic Cancer. MOJ immunology. 2018 6(2):34-42. PMID: 30637330. PMCID: PMC6329475.
- Lamichhane P, Karyampudi L, Shreeder B, [et al., including Cannon MJ]. IL10 Release upon PD-1 Blockade Sustains Immunosuppression in Ovarian Cancer. Cancer research. 2017 77(23):6667-6678. PMID: 28993412. PMCID: PMC5712245.
- Allam H, Johnson BP, Zhang M, [et al., including Cannon MJ]. The glycosyltransferase GnT-III activates Notch signaling and drives stem cell expansion to promote the growth and invasion of ovarian cancer. The Journal of biological chemistry. 2017 292(39):16351-16359. PMID: 28842505. PMCID: PMC5625063.
- Nounamo B, Liem J, Cannon M, Liu J. Myxoma Virus Optimizes Cisplatin for the Treatment of Ovarian Cancer InÂ Vitro and in a Syngeneic Murine Dissemination Model. Molecular therapy oncolytics. 2017 6:90-99. PMID: 28875159. PMCID: PMC5573804.