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Biography

Dr. Locke Bryan is an award-winning medical hematologist-oncologist at the Georgia Cancer Center who specializes in Internal Medicine as well as Lymphomas Immunotherapy Novel Therapeutics.

His work has been published in numerous journals and garnered him accolades from various organizations, including the University of Mississippi School of Medicine and the American Society of Hematology Trainee Council.

Areas of Expertise

Lymphomas Immunotherapy Novel Therapeutics

Cancer

Accomplishments

AACR/ASCO Vail Workshop

Methods in Clinical Cancer Research

Appointee

American Society of Hematology Trainee Council

University of Mississippi SOM Dean's Summer Student Research Fellowship

University of Mississippi School of Medicine

Education

University of Mississippi

Doctor of Medicine

American Board of Internal Medicine (ABIM)

Medical Oncology

American Board of Internal Medicine (ABIM)

Hematology

American Board of Internal Medicine (ABIM)

Internal Medicine

Georgia Composite Medical Board

PHY

Georgia Composite Medical Board

Georgia Medical License

Articles

Adjuvant IL-7 potentiates adoptive T cell therapy by amplifying and sustaining polyfunctional antitumor CD4+ T cells

Scientific Reports

Zhi-Chun Ding, Tsadik Habtetsion, Yang Cao, Tao Li, Chufeng Liu, Michal Kuczma, Tingting Chen, Zhonglin Hao, Locke Bryan, David H. Munn & Gang Zhou

2017-09-22

Increased availability of homeostatic cytokines is considered a major mechanism by which lymphodepletion enhances the efficacy of adoptive T cell therapy (ACT). IL-7 is one such cytokine capable of augmenting the function of tumor-reactive CD8+ T cells. However, whether host-derived IL-7 plays a role in driving the proper function of CD4+ T cells in an ACT setting remains unclear. Here we report that lymphodepleting chemotherapy by cyclophosphamide (CTX) does not lead to increased availability of the endogenous IL-7 in mice. Despite of a paucity of IL-7 in the immune milieu, CTX preconditioning allowed adoptively transferred naïve tumor-specific CD4+ T cells to undergo effector differentiation and regain IL-7Rα expression, giving rise to IL-7-responsive polyfunctional CD4+ effector cells. Correspondingly, supplementation of exogenous recombinant IL-7 markedly amplified and sustained polyfunctional CD4+ effector cells, resulting in improved therapeutic outcome in a mouse lymphoma model. We further demonstrated that the immune-enhancing effects of IL-7 were also applicable to donor CD4+ T cells pre-activated under Th1 polarizing condition. These findings suggest caution in relying on the endogenous IL-7 to enhance donor T cell expansion and persistence after lymphodepleting chemotherapy, and highlight the usefulness of recombinant IL-7 as an adjuvant for adoptive immunotherapy.

Lack of adequate pneumococcal vaccination response in chronic lymphocytic leukaemia patients receiving ibrutinib

National Library of Medicine

Benjamin Andrick, Abdulrahman Alwhaibi, David L DeRemer, Sameera Quershi, Rahil Khan, Locke J. Bryan, Payaningal R Somanath, Jeremy Pantin

2017-07-02

No abstract available

The impact of antibiotic usage on the efficacy of chemoimmunotherapy is contingent on the source of tumor-reactive T cells

U.S. National Library of Medicine

Michal P. Kuczma,1,6 Zhi-Chun Ding,1 Tao Li,2 Tsadik Habtetsion,1 Tingting Chen,1 Zhonglin Hao,1 Locke Bryan,3 Nagendra Singh,4 James N. Kochenderfer,5 and Gang Zhou1

2017-12-19

In recent years the combined use of chemotherapy and immunotherapy, collectively termed chemoimmunotherapy, has emerged as a promising treatment option for patients with cancer. Antibiotics are commonly used to reduce infection-related complications in patients undergoing chemotherapy. Intriguingly, accumulating evidence has implicated gut microbiota as a critical determinant of host antitumor immune responses, raising the question as to whether the use of broad-spectrum antibiotics would invariably diminish tumor response to chemoimmunotherapies. We investigated the impact of antibiotics on the therapeutic outcomes of cyclophosphamide (CTX) chemotherapy and adoptive T-cell therapy (ACT) where CTX was used as the host-conditioning regimen in mice. We show that antibiotic prophylaxis dampened the endogenous T cell responses elicited by CTX, and reduced the efficacy of CTX against B-cell lymphoma. In the ACT setting, antibiotics administration impaired the therapeutic effects of adoptively transferred tumor-specific CD4+ T cells in mice with implanted colorectal tumors. In contrast, long-term antibiotic exposure did not affect the efficacy of ACT using CD19-targeting chimeric antigen receptor (CAR) T cells in mice with systemic B-cell lymphoma, although it correlated with prolonged CAR expression and sustained B-cell aplasia. Our study demonstrates that chemoimmunotherapies may have variable reliance on intestinal microbiota for T cell activation and function, and thus have different sensitivities to antibiotic prophylaxis. These findings may have implications for the judicial use of antibiotics in cancer patients receiving chemoimmunotherapies.

Persistent indolent pancolonic marginal zone lymphoma of MALT-type with plasmacytic differentiation – A rare post-transplant lymphoma?

U.S. National Library of Medicine

Joanna M. Chaffin,a,* Natasha M. Savage,a Suash Sharma,a Locke J. Bryan,b Mark Raffeld,c and Elaine S. Jaffec

2017-11-10

Marginal zone lymphoma of mucosa-associated lymphoid tissue (MALT lymphoma) is associated with chronic inflammatory disorders. We present an indolent pancolonic MALT lymphoma occurring in a 39-year-old female with history of autoimmune hepatitis requiring liver transplant in 1997 and ulcerative colitis diagnosed in 2004. Random biopsies from a grossly unremarkable surveillance colonoscopy in 2015 revealed a dense monomorphic plasmacytoid infiltrate causing expansion of lamina propria without significant crypt infiltration or destruction. These cells were positive for CD79a and CD138 and showed lambda restriction; however, CD20, CD43, CD56, HHV8, and EBER were negative. A similar pancolonic infiltrate was identified in all prior colorectal biopsies from 2010 and 2012 upon retrospective review. Subsequent computed tomography of the abdomen revealed no bowel wall thickening nor enlarged lymph nodes. Bone marrow revealed involvement consistent with stage IV disease. Biopsies from 2010 and 2015 demonstrated clonal immunoglobulin gene rearrangement. MYD88 mutation was not detected. The overall features were indicative of MALT lymphoma. Although low-grade B-cell lymphomas are not considered part of the post-transplant lymphoproliferative disorder spectrum, such cases have been reported, and are typically EBV-negative. Patient underwent treatment with pentostatin for her MALT lymphoma reaching a sustained remission despite additional immunosuppression for resurgent hepatic dysfunction. To our knowledge, this is the first reported case of EBV-negative pancolonic MALT lymphoma with plasmacytic differentiation post liver transplant presenting in an indolent, asymptomatic fashion with persistence for greater than five years successfully managed without compromising the patient’s liver transplant.