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DeVito, Nicholas Christian

Overview:

I am an instructor of Medical Oncology who primarily treats patients with gastrointestinal malignancies. My research focused on tumor immune evasion and immunotherapy.

Positions:

Medical Instructor in the Department of Medicine

Medicine, Medical Oncology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2012

M.D. — University of South Florida College of Medicine

Internal Medicine Internship and Residency

Tufts University School of Medicine

Hematology-Oncology Fellowship, Medicine

Duke University School of Medicine

Grants:

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

Administered By
Medicine, Medical Oncology
AwardedBy
Damon Runyon Cancer Research Foundation
Role
PI-Fellow
Start Date
July 01, 2018
End Date
June 30, 2019

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

Administered By
Medicine, Medical Oncology
AwardedBy
Conquer Cancer Foundation
Role
PI-Fellow
Start Date
July 01, 2017
End Date
June 30, 2018

Publications:

Checkpoint inhibitor use in two heart transplant patients with metastatic melanoma and review of high-risk populations.

Due to the unique side-effect profile of immune checkpoint inhibitors (ICIs), groups of patients deemed to be at high risk of complications were excluded from trials that proved the efficacy and safety of these agents in patients with various malignancies. Among these excluded patients were those with prior solid organ transplantation, chronic viral infections and pre-existing autoimmune diseases including paraneoplastic syndromes. We present follow-up on a patient from a previously published case report with an orthotopic heart transplantation who was treated with both cytotoxic T-lymphocyte antigen 4 and PD-1 inhibition safely, without organ rejection. Additionally, we describe the case of a patient with a cardiac allograft who also did not experience organ rejection after treatment with pembrolizumab. Through smaller trials, retrospective analyses, case series and individual case reports, we are accumulating initial data on how these agents are tolerated by the aforementioned groups. Our survey of the literature has found more evidence of organ transplant rejection in patients treated with PD-1 inhibitors than those treated with inhibitors of cytotoxic T-lymphocyte antigen 4. Patients with chronic viral infections, especially hepatitis C, seem to have little to no risk of treatment-related increase in serum RNA levels. The literature contains few documented cases of devastating exacerbations of pre-existing autoimmune disease during treatment with ICIs, and flares seem to be easily controlled by immunosuppression in the vast majority of cases. Last, several cases allude to a promising role for disease-specific antibodies and other serum biomarkers in identifying patients at high risk of developing certain immune-related adverse events, detecting subclinical immune-related adverse event onset, and monitoring treatment response to immunosuppressive therapy in patients treated with ICIs. Though these excluded populations have not been well studied in randomized placebo-controlled trials, we may be able to learn and derive hypotheses from the existing observational data in the literature.

Authors
Grant, MJ; DeVito, N; Salama, AKS
MLA Citation
Grant, MJ, DeVito, N, and Salama, AKS. "Checkpoint inhibitor use in two heart transplant patients with metastatic melanoma and review of high-risk populations.(Accepted)" Melanoma Management 5.4 (December 2018): MMT10-null. (Review)
PMID
30459942
Source
epmc
Published In
Melanoma Management
Volume
5
Issue
4
Publish Date
2018
Start Page
MMT10
DOI
10.2217/mmt-2018-0004

Stromal Fibroblasts Mediate Anti-PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma.

Although anti-PD-1 therapy has improved clinical outcomes for select patients with advanced cancer, many patients exhibit either primary or adaptive resistance to checkpoint inhibitor immunotherapy. The role of the tumor stroma in the development of these mechanisms of resistance to checkpoint inhibitors remains unclear. We demonstrated that pharmacologic inhibition of the TGFβ signaling pathway synergistically enhanced the efficacy of anti-CTLA-4 immunotherapy but failed to augment anti-PD-1/PD-L1 responses in an autochthonous model of BRAFV600E melanoma. Additional mechanistic studies revealed that TGFβ pathway inhibition promoted the proliferative expansion of stromal fibroblasts, thereby facilitating MMP-9-dependent cleavage of PD-L1 surface expression, leading to anti-PD-1 resistance in this model. Further work demonstrated that melanomas escaping anti-PD-1 therapy exhibited a mesenchymal phenotype associated with enhanced TGFβ signaling activity. Delayed TGFβ inhibitor therapy, following anti-PD-1 escape, better served to control further disease progression and was superior to a continuous combination of anti-PD-1 and TGFβ inhibition. This work illustrates that formulating immunotherapy combination regimens to enhance the efficacy of checkpoint blockade requires an in-depth understanding of the impact of these agents on the tumor microenvironment. These data indicated that stromal fibroblast MMP-9 may desensitize tumors to anti-PD-1 and suggests that TGFβ inhibition may generate greater immunologic efficacy when administered following the development of acquired anti-PD-1 resistance. Cancer Immunol Res; 1-13. ©2018 AACR.

Authors
Zhao, F; Evans, K; Xiao, C; DeVito, N; Theivanthiran, B; Holtzhausen, A; Siska, PJ; Blobe, GC; Hanks, BA
MLA Citation
Zhao, F, Evans, K, Xiao, C, DeVito, N, Theivanthiran, B, Holtzhausen, A, Siska, PJ, Blobe, GC, and Hanks, BA. "Stromal Fibroblasts Mediate Anti-PD-1 Resistance via MMP-9 and Dictate TGFβ Inhibitor Sequencing in Melanoma." Cancer Immunology Research (September 12, 2018).
Website
https://hdl.handle.net/10161/17694
PMID
30209062
Source
epmc
Published In
Cancer Immunology Research
Publish Date
2018
DOI
10.1158/2326-6066.cir-18-0086

Paracrine Wnt5a-β-Catenin Signaling Triggers a Metabolic Program that Drives Dendritic Cell Tolerization.

Despite recent advances, many cancers remain refractory to available immunotherapeutic strategies. Emerging evidence indicates that the tolerization of local dendritic cells (DCs) within the tumor microenvironment promotes immune evasion. Here, we have described a mechanism by which melanomas establish a site of immune privilege via a paracrine Wnt5a-β-catenin-peroxisome proliferator-activated receptor-γ (PPAR-γ) signaling pathway that drives fatty acid oxidation (FAO) in DCs by upregulating the expression of the carnitine palmitoyltransferase-1A (CPT1A) fatty acid transporter. This FAO shift increased the protoporphyrin IX prosthetic group of indoleamine 2,3-dioxgenase-1 (IDO) while suppressing interleukin(IL)-6 and IL-12 cytokine expression, culminating in enhanced IDO activity and the generation of regulatory T cells. We demonstrated that blockade of this pathway augmented anti-melanoma immunity, enhanced the activity of anti-PD-1 antibody immunotherapy, and suppressed disease progression in a transgenic melanoma model. This work implicates a role for tumor-mediated metabolic reprogramming of local DCs in immune evasion and immunotherapy resistance.

Authors
Zhao, F; Xiao, C; Evans, KS; Theivanthiran, T; DeVito, N; Holtzhausen, A; Liu, J; Liu, X; Boczkowski, D; Nair, S; Locasale, JW; Hanks, BA
MLA Citation
Zhao, F, Xiao, C, Evans, KS, Theivanthiran, T, DeVito, N, Holtzhausen, A, Liu, J, Liu, X, Boczkowski, D, Nair, S, Locasale, JW, and Hanks, BA. "Paracrine Wnt5a-β-Catenin Signaling Triggers a Metabolic Program that Drives Dendritic Cell Tolerization." Immunity 48.1 (January 2018): 147-160.e7.
Website
https://hdl.handle.net/10161/17695
PMID
29343435
Source
epmc
Published In
Immunity
Volume
48
Issue
1
Publish Date
2018
Start Page
147
End Page
160.e7
DOI
10.1016/j.immuni.2017.12.004

Paraneoplastic Production of Granulocyte-macrophage Colony-stimulating Factor and Granulocyte Colony-stimulating Factor in a Case of Rapidly Progressing Cutaneous Squamous Cell Carcinoma

Authors
Kinsey, EN; DeVito, N; Barrow, W; Myers, SA; Salama, AK
MLA Citation
Kinsey, EN, DeVito, N, Barrow, W, Myers, SA, and Salama, AK. "Paraneoplastic Production of Granulocyte-macrophage Colony-stimulating Factor and Granulocyte Colony-stimulating Factor in a Case of Rapidly Progressing Cutaneous Squamous Cell Carcinoma." Clinical Skin Cancer 1.1 (January 2016): 20-22.
Source
crossref
Volume
1
Issue
1
Publish Date
2016
Start Page
20
End Page
22
DOI
10.1016/j.clsc.2016.11.004

Clinical Characteristics and Outcomes for Solitary Fibrous Tumor (SFT): A Single Center Experience.

Solitary fibrous tumor (SFT) is a mesenchymal neoplasm of fibrous origin. The 2013 WHO classification of soft tissue tumors defines malignant forms as hypercellular, mitotically active (>4 mitosis/10 high-power fields), with cytological atypia, tumor necrosis, and/or infiltrative margins. With an IRB-approved protocol, we investigated patient records and clinicopathologic data from our Sarcoma Database to describe the clinical characteristics of both benign and malignant SFT. All pathology specimens were reviewed by two pathologists. Descriptive statistics and univariate/multivariate survival analysis were performed. Patient records and Social Security Death Index were used to evaluate vital status. Of 82 patients, 47 (57%) were women and 73 (89%) were Caucasian. Median age was 62 years (range, 20 to 89). Thirty-two (39%) patients succumbed to the disease. Primary tumor site was lung/pleura in 28 (34%), abdomen/pelvis in 23 (28%), extremity in 13 (16%), and head/neck in 9 (11%) patients. Pathology was described as benign in 42 (51%) and malignant in 40 (49%) patients. Compared to benign SFT, malignant histology is associated with larger tumor size, higher mitotic counts, metastatic disease at diagnosis, and greater use of chemotherapy and radiation therapy. Gender, age, and tumor site were not significantly different between benign and malignant subtypes. By univariate analysis, only benign vs. malignant variant and complete resection positively impacted overall survival (P = 0.02 and P<0.0001, respectively). In the multivariable analysis of overall survival, receiving chemotherapy or not receiving surgery were two variables significantly associated with higher failure rate in overall survival: patients with chemotherapy vs. no chemotherapy (P = 0.003, HR = 4.55, with 95% CI: 1.68-12.34) and patients without surgery vs. with surgery (P = 0.005, HR = 25.49, with 95% CI: 2.62-247.57). Clear survival differences exist between benign and malignant SFT. While surgery appears to be the best treatment option for benign and malignant SFT, better systemic therapies are needed to improve outcomes of patients with metastatic, malignant SFT.

Authors
DeVito, N; Henderson, E; Han, G; Reed, D; Bui, MM; Lavey, R; Robinson, L; Zager, JS; Gonzalez, RJ; Sondak, VK; Letson, GD; Conley, A
MLA Citation
DeVito, N, Henderson, E, Han, G, Reed, D, Bui, MM, Lavey, R, Robinson, L, Zager, JS, Gonzalez, RJ, Sondak, VK, Letson, GD, and Conley, A. "Clinical Characteristics and Outcomes for Solitary Fibrous Tumor (SFT): A Single Center Experience." Plos One 10.10 (January 2015): e0140362-null.
PMID
26469269
Source
epmc
Published In
Plos One
Volume
10
Issue
10
Publish Date
2015
Start Page
e0140362
DOI
10.1371/journal.pone.0140362

Small lymphocytic lymphoma presenting as a paraneoplastic syndrome with acute central nervous system demyelination.

Authors
DeVito, N; Mui, K; Jassam, Y; Taylor, L; Pilichowska, M; Cossor, F
MLA Citation
DeVito, N, Mui, K, Jassam, Y, Taylor, L, Pilichowska, M, and Cossor, F. "Small lymphocytic lymphoma presenting as a paraneoplastic syndrome with acute central nervous system demyelination." Clinical Lymphoma, Myeloma & Leukemia 14.4 (August 2014): e131-e135.
PMID
24630921
Source
epmc
Published In
Clinical Lymphoma, Myeloma & Leukemia
Volume
14
Issue
4
Publish Date
2014
Start Page
e131
End Page
e135
DOI
10.1016/j.clml.2014.02.006

LITTLE KNOWN LYMPHOMA: SMALL LYMPHOCYTIC LYMPHOMA PRESENTING AS A PARANEOPLASTIC SYNDROME WITH ACUTE CNS DEMYELINATION

Authors
DeVito, N
MLA Citation
DeVito, N. "LITTLE KNOWN LYMPHOMA: SMALL LYMPHOCYTIC LYMPHOMA PRESENTING AS A PARANEOPLASTIC SYNDROME WITH ACUTE CNS DEMYELINATION." 37th Annual Meeting of the Society-General-Internal-Medicine. April 23, 2014 - April 26, 2014. San Diego, CA.: SPRINGER, April 1, 2014.
Source
wos
Published In
Journal of General Internal Medicine
Volume
29
Publish Date
2014
Start Page
S384
End Page
S384

Advances in immunotherapy for pancreatic cancer: 2013.

Pancreatic cancer is one of the more difficult malignancies to treat, and there is a great need for less toxic, effective regimens. Immunotherapy has shown potential in the treatment of pancreatic cancer, and at ASCO 2013 there were several progressive advances in its clinical application. Abstracts #3067, #3049, #3007, #4040, #LBA4004, and #3090 will be discussed. New developments in the field of immunotherapy are promising novel treatments for pancreatic neoplasms with tolerable side effect profiles.

Authors
DeVito, NC; Saif, MW
MLA Citation
DeVito, NC, and Saif, MW. "Advances in immunotherapy for pancreatic cancer: 2013." Jop : Journal of the Pancreas 14.4 (July 10, 2013): 347-353.
PMID
23846925
Source
epmc
Published In
Jop : Journal of the Pancreas
Volume
14
Issue
4
Publish Date
2013
Start Page
347
End Page
353
DOI
10.6092/1590-8577/1646

Retrospective study of patients with brain metastases from melanoma receiving concurrent whole-brain radiation and temozolomide.

Metastatic melanoma is the second most common cancer to metastasize to the brain. It is typically treated using stereotactic radiosurgery with or without whole-brain radiation (WBR) therapy. Recently, the alkylating agent temozolomide, which has demonstrated activity in patients with brain metastasis and primary tumors, was used alongside WBR to delay brain metastasis recurrence, increase survival, and improve quality-of-life in patients with brain metastases.In this retrospective study, we reviewed outcomes of 29 patients treated from 2005-2009 at the Moffitt Cancer Center with brain metastases of melanoma. Results were narrowed via retrospective chart analysis to a cohort with brain metastasis receiving concomitant temozolomide and WBR.Median progression-free survival was 20.4 weeks and overall survival was 44.4 weeks compared to 16 week survival of patients treated with WBR alone.A prospective trial evaluating this combined regimen may be considered.

Authors
Devito, N; Yu, M; Chen, R; Pan, E
MLA Citation
Devito, N, Yu, M, Chen, R, and Pan, E. "Retrospective study of patients with brain metastases from melanoma receiving concurrent whole-brain radiation and temozolomide." Anticancer Research 31.12 (December 2011): 4537-4543.
PMID
22199328
Source
epmc
Published In
Anticancer Research
Volume
31
Issue
12
Publish Date
2011
Start Page
4537
End Page
4543

In vivo expansion, persistence, and function of peptide vaccine-induced CD8 T cells occur independently of CD4 T cells.

Significant efforts are being devoted toward the development of effective therapeutic vaccines against cancer. Specifically, well-characterized subunit vaccines, which are designed to generate antitumor cytotoxic CD8 T-cell responses. Because CD4 T cells participate at various stages of CD8 T-cell responses, it is important to study the role of CD4 T cells in the induction and persistence of antitumor CD8 T-cell responses by these vaccines. Recent evidence points to the requirement of CD4 T cells for the long-term persistence of memory CD8 T cells, which in the case of cancer immunotherapy would be critical for the prevention of tumor recurrences. The purpose of the present study was to assess whether CD4 T cells are necessary for the generation and maintenance of antigen-specific CD8 T cells induced by subunit (peptide or DNA) vaccines. We have used a vaccination strategy that combines synthetic peptides representing CD8 T-cell epitopes, a costimulatory anti-CD40 antibody and a Toll-like receptor agonist (TriVax) to generate large numbers of antigen-specific CD8 T-cell responses. Our results show that the rate of decline (clonal contraction) of the antigen-specific CD8 T cells and their functional state is not affected by the presence or absence of CD4 T cells throughout the immune response generated by TriVax. We believe that these results bear importance for the design of effective vaccination strategies against cancer.

Authors
Assudani, D; Cho, H-I; DeVito, N; Bradley, N; Celis, E
MLA Citation
Assudani, D, Cho, H-I, DeVito, N, Bradley, N, and Celis, E. "In vivo expansion, persistence, and function of peptide vaccine-induced CD8 T cells occur independently of CD4 T cells." Cancer Research 68.23 (December 2008): 9892-9899.
PMID
19047170
Source
epmc
Published In
Cancer Research
Volume
68
Issue
23
Publish Date
2008
Start Page
9892
End Page
9899
DOI
10.1158/0008-5472.CAN-08-3134

Inflammasome-Wnt Ligand Signaling Axis Promotes Immune Escape During Anti-PD-1 Antibody Immunotherapy

Authors
Thievanthiran, B; DeVito, N; Evans, K; Hanks, BA
MLA Citation
Thievanthiran, B, DeVito, N, Evans, K, and Hanks, BA. "Inflammasome-Wnt Ligand Signaling Axis Promotes Immune Escape During Anti-PD-1 Antibody Immunotherapy." 2018 Society for Immunotherapy of Cancer Annual Meeting. November 7, 2018 - November 11, 2018. Washington, DC.: BioMed Central,.
Source
manual
Published In
Journal for Immunotherapy of Cancer
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