Brent Hanks

Overview:

We are interested in understanding the mechanisms that cancers have evolved to suppress the generation of tumor antigen-specific immune responses and how this knowledge can be exploited for the development of novel and more effective cancer immunotherapy strategies. This work involves the utilization of both autochthonous transgenic tumor model systems as well as clinical specimens to develop novel strategies to enhance the efficacy of immunotherapies while also developing predictive biomarkers to better guide the management of cancer patients with these agents. We strive to translate our understanding of the fundamental biochemical and metabolic pathways within the tumor microenvironment that are critical for driving immune evasion and resistance into early phase clinical trial testing.

Our work utilizes a variety of techniques and methodologies that span the breadth of basic biological research. This work integrates studies based on both 1) transgenic mouse tumor models that are monitored using bioluminescence and micro-CT imaging and 2) a variety of clinical specimens.

Our current areas of focus include:

  1. Investigating mechanisms of adaptive or acquired immunotherapy resistance in cancer
  2. Studying the relationship between EMT pathways and immunotherapy resistance.
  3. Elucidating mechanisms of dendritic cell tolerization in the tumor microenvironment and how these processes may contribute to immunotherapy resistance
  4. Development of novel pharmacologic and genetic strategies to overcome immunotherapy resistance
  5. Investigating mechanisms contributing to select immunotherapy-associated toxicities

Positions:

Associate Professor of Medicine

Medicine, Medical Oncology
School of Medicine

Assistant Professor of Pharmacology and Cancer Biology

Pharmacology & Cancer Biology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

Ph.D. 2004

Baylor College of Medicine

M.D. 2006

Baylor College of Medicine

Internship and Residency, Internal Medicine

Duke University School of Medicine

Fellowship, Hematology/Oncology

Duke University School of Medicine

Grants:

Therapeutic Targeting of the TGF-beta Signaling Axis to Modulate the Tumor Immune Microenvironment and Enhance Melanoma Immunotherapy

Administered By
Medicine, Medical Oncology
Awarded By
Melanoma Research Alliance
Role
Principal Investigator
Start Date
End Date

Role of Type III TGF-b Receptor in Mediating Immunosuppression During Breast Cancer Progression

Administered By
Medicine, Medical Oncology
Awarded By
Department of Defense
Role
Principal Investigator
Start Date
End Date

Investigating the Role of EMT-mediated Dendritic Cell Tolerization in Checkpoint Inhibitor Resistance

Administered By
Medicine, Medical Oncology
Awarded By
Damon Runyon Cancer Research Foundation
Role
Principal Investigator
Start Date
End Date

Investigating Oncogenic Signaling Pathways that Drive Wnt Ligand-mediated Immune Tolerance in Melanoma

Administered By
Medicine, Medical Oncology
Awarded By
Conquer Cancer Foundation
Role
Principal Investigator
Start Date
End Date

HSP70-TLR4-mediated MDSC Recruitment as an Adaptive Resistance

Administered By
Medicine, Medical Oncology
Awarded By
Merck Sharp & Dohme
Role
Principal Investigator
Start Date
End Date

Publications:

Supplementary Table S3 from APOBEC Mutagenesis Inhibits Breast Cancer Growth through Induction of T cell–Mediated Antitumor Immune Responses

<jats:p>&lt;p&gt;Supplementary Table S3&lt;/p&gt;</jats:p>
Authors
DiMarco, AV; Qin, X; McKinney, BJ; Garcia, NMG; Van Alsten, SC; Mendes, EA; Force, J; Hanks, BA; Troester, MA; Owzar, K; Xie, J; Alvarez, JV
MLA Citation
URI
https://scholars.duke.edu/individual/pub1571581
Source
crossref
Published Date
DOI
10.1158/2326-6066.22544469

Supplementary Table 1 from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

<jats:p>&lt;p&gt;qRT-PCR primers used in the current study.&lt;/p&gt;</jats:p>
Authors
Zhao, F; Evans, K; Xiao, C; DeVito, N; Theivanthiran, B; Holtzhausen, A; Siska, PJ; Blobe, GC; Hanks, BA
MLA Citation
URI
https://scholars.duke.edu/individual/pub1571591
Source
crossref
Published Date
DOI
10.1158/2326-6066.22539827.v1

Data from APOBEC Mutagenesis Inhibits Breast Cancer Growth through Induction of T cell–Mediated Antitumor Immune Responses

<jats:p>&lt;div&gt;Abstract&lt;p&gt;The APOBEC family of cytidine deaminases is one of the most common endogenous sources of mutations in human cancer. Genomic studies of tumors have found that APOBEC mutational signatures are enriched in the HER2 subtype of breast cancer and are associated with immunotherapy response in diverse cancer types. However, the direct consequences of APOBEC mutagenesis on the tumor immune microenvironment have not been thoroughly investigated. To address this, we developed syngeneic murine mammary tumor models with inducible expression of APOBEC3B. We found that APOBEC activity induced antitumor adaptive immune responses and CD4&lt;sup&gt;+&lt;/sup&gt; T cell–mediated, antigen-specific tumor growth inhibition. Although polyclonal APOBEC tumors had a moderate growth defect, clonal APOBEC tumors were almost completely rejected, suggesting that APOBEC-mediated genetic heterogeneity limits antitumor adaptive immune responses. Consistent with the observed immune infiltration in APOBEC tumors, APOBEC activity sensitized HER2-driven breast tumors to anti–CTLA-4 checkpoint inhibition and led to a complete response to combination anti–CTLA-4 and anti-HER2 therapy. In human breast cancers, the relationship between APOBEC mutagenesis and immunogenicity varied by breast cancer subtype and the frequency of subclonal mutations. This work provides a mechanistic basis for the sensitivity of APOBEC tumors to checkpoint inhibitors and suggests a rationale for using APOBEC mutational signatures and clonality as biomarkers predicting immunotherapy response in HER2-positive (HER2&lt;sup&gt;+&lt;/sup&gt;) breast cancers.&lt;/p&gt;&lt;/div&gt;</jats:p>
Authors
DiMarco, AV; Qin, X; McKinney, BJ; Garcia, NMG; Van Alsten, SC; Mendes, EA; Force, J; Hanks, BA; Troester, MA; Owzar, K; Xie, J; Alvarez, JV
MLA Citation
DiMarco, Ashley V., et al. Data from APOBEC Mutagenesis Inhibits Breast Cancer Growth through Induction of T cell–Mediated Antitumor Immune Responses. 4 Apr. 2023. Crossref, doi:10.1158/2326-6066.c.6550653.v1.
URI
https://scholars.duke.edu/individual/pub1571583
Source
crossref
Published Date
DOI
10.1158/2326-6066.c.6550653.v1

Supplementary Figure S5 from Stromal Fibroblasts Mediate Anti–PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma

<jats:p>&lt;p&gt;Effect of melanoma-associated fibroblast MMP9 on immune responses to anti-PD1 therapy.&lt;/p&gt;</jats:p>
Authors
Zhao, F; Evans, K; Xiao, C; DeVito, N; Theivanthiran, B; Holtzhausen, A; Siska, PJ; Blobe, GC; Hanks, BA
MLA Citation
URI
https://scholars.duke.edu/individual/pub1571592
Source
crossref
Published Date
DOI
10.1158/2326-6066.22539839

Supplementary Data Legends from APOBEC Mutagenesis Inhibits Breast Cancer Growth through Induction of T cell–Mediated Antitumor Immune Responses

<jats:p>&lt;p&gt;Legends for Figures S1-S11 and Supplementary Tables S1-S3&lt;/p&gt;</jats:p>
Authors
DiMarco, AV; Qin, X; McKinney, BJ; Garcia, NMG; Van Alsten, SC; Mendes, EA; Force, J; Hanks, BA; Troester, MA; Owzar, K; Xie, J; Alvarez, JV
MLA Citation
URI
https://scholars.duke.edu/individual/pub1571585
Source
crossref
Published Date
DOI
10.1158/2326-6066.22544478

Research Areas:

Biomarkers, Pharmacological
Cell Line, Tumor
Chemokine CCL22
Combined Modality Therapy
Dendritic Cells
Disease-Free Survival
Down-Regulation
Female
Humans
Indoleamine-Pyrrole 2,3,-Dioxygenase
Lymphocyte Activation
Mammary Neoplasms, Experimental
Melanoma
Melanoma, Experimental
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Mice, Transgenic
Molecular Targeted Therapy
Neoplasm Staging
Neoplasm Transplantation
Neoplasms
Prognosis
Proteoglycans
Receptors, Transforming Growth Factor beta
Signal Transduction
Transforming Growth Factor beta
Tumor Escape
Tumor Microenvironment
Associate Professor of Medicine

Contact:

Profile

https://scholars.duke.edu/person/hanks004

Email

hanks004@mc.duke.edu
308 Research Drive, Lsrc, Room C162, Durham, NC 27708
Lsrc, Box 91004, Pharmacology and Cancer Biology, Durham, NC 27708