Peter Fecci

Overview:

As the Director of both the Brain Tumor Immunotherapy Program and the Center for Brain and Spine Metastasis at Duke University, I focus our programmatic interests on the design, optimization, and monitoring of immune-based treatment platforms for patients with intracranial tumors, whether primary or metastatic. Within this broad scope, however, my own group looks more specifically at limitations to immunotherapeutic success, with a particular focus on understanding and reversing T cell dysfunction in patients with glioblastoma (GBM) and brain metastases. We employ a systematic approach to categorizing T cell dysfunction (Woroniecka et al, Clin Cancer Res 2018 Aug 15;24(16):3792-3802), and whereas our earlier work addressed concerns for regulatory T cell-induced tolerance, we now heavily study T cell ignorance and exhaustion, as well. Regarding the former, we recently published the novel phenomenon of S1P1-mediated bone marrow T cell sequestration in patients with intracranial tumors (Chongsathidkiet et al, Nat Medicine 2018 Sep;24(9):1459-1468). Regarding the latter, we have likewise recently identified and characterized exhaustion as a significant limitation to T-cell function within GBM (Woroniecka et al, Clin Cancer Res 2018 Sep 1;24(17):4175-4186). I very much look to collaboratively integrate our approaches with others investigating innovative treatment options. I continue my focus on combining strategies for reversing T cell deficits with current and novel immune-based platforms as a means of deriving and improving rational and precise anti-tumor therapies. It is my sincerest desire to forge a career focused on co-operative, multi-disciplinary, organized brain tumor therapy. Ultimately, my goal is to help coordinate the efforts of a streamlined and effective center for brain tumor research and clinical care. I hope to play some role in ushering in a period where the science and treatment arms of brain tumor therapy suffer no disjoint, but instead represent the convergent efforts of researchers, neuro-oncologists, medical oncologists, radiation oncologists, biomedical engineers, and neurosurgeons alike. I hope to see such synergy become standard of care.

Positions:

Associate Professor of Neurosurgery

Neurosurgery
School of Medicine

Associate Professor in Immunology

Immunology
School of Medicine

Associate Professor in Pathology

Pathology
School of Medicine

Member of the Duke Cancer Institute

Duke Cancer Institute
School of Medicine

Education:

M.D. 2007

Duke University School of Medicine

Ph.D. 2007

Duke University

Internship, General Surgery

Massachusetts General Hospital

Residency, Neurosurgery

Massachusetts General Hospital

Postdoctoral Fellow

Dana-Farber Cancer Institute

Instructor, Neurosurgery

Massachusetts General Hospital

Grants:

Laser Ablation of Abnormal Neurolgoical Tissue using Robotic Neuroblate System (LAANTERN) Prospective Registry

Administered By
Neurosurgery
Awarded By
Monteris Medical, Inc.
Role
Principal Investigator
Start Date
End Date

NINDS Research Education Programs for Residents and Fellows in Neurosurgery

Administered By
Neurosurgery
Awarded By
National Institutes of Health
Role
Principal Investigator
Start Date
End Date

LITT and Short Course Radiation for Patients with GBM Requiring Standard Treatment Alternatives (LASR)

Administered By
Duke Cancer Institute
Awarded By
Monteris Medical, Inc.
Role
Principal Investigator
Start Date
End Date

Directed Chemotherapy Delivery for Leptomeningeal Metastases

Administered By
Neurosurgery
Awarded By
Minnetronix, Inc
Role
Co Investigator
Start Date
End Date

Validation of Novel Therapeutic Approach for Leptomeningeal Metastases

Administered By
Neurosurgery
Awarded By
Minnetronix, Inc
Role
Co Investigator
Start Date
End Date

Publications:

CD4 T-Cell Exhaustion: Does It Exist and What Are Its Roles in Cancer?

In chronic infections and in cancer, persistent antigen stimulation under suboptimal conditions can lead to the induction of T-cell exhaustion. Exhausted T cells are characterized by an increased expression of inhibitory markers and a progressive and hierarchical loss of function. Although cancer-induced exhaustion in CD8 T cells has been well-characterized and identified as a therapeutic target (i.e., via checkpoint inhibition), in-depth analyses of exhaustion in other immune cell types, including CD4 T cells, is wanting. While perhaps attributable to the contextual discovery of exhaustion amidst chronic viral infection, the lack of thorough inquiry into CD4 T-cell exhaustion is particularly surprising given their important role in orchestrating immune responses through T-helper and direct cytotoxic functions. Current work suggests that CD4 T-cell exhaustion may indeed be prevalent, and as CD4 T cells have been implicated in various disease pathologies, such exhaustion is likely to be clinically relevant. Defining phenotypic exhaustion in the various CD4 T-cell subsets and how it influences immune responses and disease severity will be crucial to understanding collective immune dysfunction in a variety of pathologies. In this review, we will discuss mechanistic and clinical evidence for CD4 T-cell exhaustion in cancer. Further insight into the derivation and manifestation of exhaustive processes in CD4 T cells could reveal novel therapeutic targets to abrogate CD4 T-cell exhaustion in cancer and induce a robust antitumor immune response.
Authors
Miggelbrink, AM; Jackson, JD; Lorrey, SJ; Srinivasan, ES; Waibl-Polania, J; Wilkinson, DS; Fecci, PE
MLA Citation
Miggelbrink, Alexandra M., et al. “CD4 T-Cell Exhaustion: Does It Exist and What Are Its Roles in Cancer?Clin Cancer Res, vol. 27, no. 21, Nov. 2021, pp. 5742–52. Pubmed, doi:10.1158/1078-0432.CCR-21-0206.
URI
https://scholars.duke.edu/individual/pub1485795
PMID
34127507
Source
pubmed
Published In
Clinical Cancer Research
Volume
27
Published Date
Start Page
5742
End Page
5752
DOI
10.1158/1078-0432.CCR-21-0206

Palliative Care Use for Critically Ill Patients With Brain Metastases.

CONTEXT: Critically ill patients with brain metastases (BM) face significant uncertainty regarding prognosis and survival and can benefit from Palliative care (PC). However, research regarding the role of PC in this population is lacking. OBJECTIVES: We sought to compare BM patients admitted to an intensive care unit who received an inpatient PC consult (PC cohort) to those who did not (Usual Care, UC cohort). METHODS: We performed a single-institution retrospective cohort analysis. Our outcome variables were mortality, time from intensive care unit admission to death, disposition, and change in code status. We also evaluated PC's role in complex medical decision making, symptom management and hospice education. RESULTS: PC consult was placed in 31 of 118 (28%) of patients. The overall mortality rates were not statistically different (78.8% vs. 90.3%, P= 0.15, UC vs. PC cohort). Patients in the PC cohort had a shorter time to death, higher rate of death within 30 days of admission, increased rate of discharge to hospice, and increase percentage of code status change to "do not attempt resuscitation" during the admission. The primary services provided by PC were symptom management (n = 21, 67.7%) and assistance in complex medical decision making (n = 20, 64.5%). CONCLUSION: In our patient cohort, PC is an underutilized service that can assist in complex medical decision making and symptom management of critically ill BM patients. Further prospective studies surveying patient, family and provider experiences could better inform the qualitative impact of PC in this unique patient population.
Authors
Kang, JH; Price, M; Dalton, T; Ramirez, L; Fecci, PE; Kamal, AH; Johnson, MO; Peters, KB; Goodwin, CR
MLA Citation
Kang, Jennifer H., et al. “Palliative Care Use for Critically Ill Patients With Brain Metastases.J Pain Symptom Manage, vol. 62, no. 5, Nov. 2021, pp. 927–35. Pubmed, doi:10.1016/j.jpainsymman.2021.05.003.
URI
https://scholars.duke.edu/individual/pub1483303
PMID
33992757
Source
pubmed
Published In
J Pain Symptom Manage
Volume
62
Published Date
Start Page
927
End Page
935
DOI
10.1016/j.jpainsymman.2021.05.003

Broad immunophenotyping of the murine brain tumor microenvironment.

Here we present a 14-color flow cytometry panel for the evaluation of 13 myeloid and lymphoid populations within murine glioblastoma samples. Reagents, processing protocols, and downstream analyses were thoroughly validated and optimized to resolve the following populations: T cells (CD4, CD8, CD3), B cells (B220), NK cells (NK1.1), neutrophils (Ly6G), classical and non-classical monocytes (Ly6c, CD43), macrophages (F4/80, CD11b), microglia (CD45-lo, CD11b), and dendritic cells (DCs) (CD11c, MHC class II). In addition, this panel leaves Alexa Fluor 488/FITC open for the inclusion of fluorescent reporters or congenic marker staining.
Authors
Tomaszewski, WH; Waibl-Polania, J; Miggelbrink, AM; Chakraborty, MA; Fecci, PE; Sampson, JH; Gunn, MD
MLA Citation
Tomaszewski, W. H., et al. “Broad immunophenotyping of the murine brain tumor microenvironment.J Immunol Methods, vol. 499, Sept. 2021, p. 113158. Pubmed, doi:10.1016/j.jim.2021.113158.
URI
https://scholars.duke.edu/individual/pub1498297
PMID
34597618
Source
pubmed
Published In
J Immunol Methods
Volume
499
Published Date
Start Page
113158
DOI
10.1016/j.jim.2021.113158

Cold-inducible RNA-binding protein (CIRBP) as a biomarker to predict recurrence of brain metastases.

Authors
Chongsathidkiet, P; Fecci, PE
MLA Citation
Chongsathidkiet, Pakawat, and Peter E. Fecci. “Cold-inducible RNA-binding protein (CIRBP) as a biomarker to predict recurrence of brain metastases.Neuro Oncol, vol. 23, no. 9, Sept. 2021, pp. 1419–20. Pubmed, doi:10.1093/neuonc/noab122.
URI
https://scholars.duke.edu/individual/pub1482815
PMID
34036364
Source
pubmed
Published In
Neuro Oncol
Volume
23
Published Date
Start Page
1419
End Page
1420
DOI
10.1093/neuonc/noab122

Inpatient palliative care utilization for patients with brain metastases.

Introduction: Given the high symptom burden and complex clinical decision making associated with a diagnosis of brain metastases (BM), specialty palliative care (PC) can meaningfully improve patient quality of life. However, no prior study has formally evaluated patient-specific factors associated with PC consultation among BM patients. Methods: We examined the rates of PC consults in a cohort of 1303 patients with BM admitted to three tertiary medical centers from October 2015 to December 2018. Patient demographics, surgical status, 30-day readmission, and death data were collected via retrospective chart review. PC utilization was assessed by identifying encounters for which an inpatient consult to PC was placed. Statistical analyses were performed to compare characteristics and outcomes between patients who did and did not receive PC consults. Results: We analyzed 1303 patients admitted to the hospital with BM. The average overall rate of inpatient PC consultation was 19.6%. Rates of PC utilization differed significantly by patient race (17.5% in White/Caucasian vs 26.0% in Black/African American patients, P = .0014). Patients who received surgery during their admission had significantly lower rates of PC consultation (3.9% vs 22.4%, P < .0001). Patients who either died during their admission or were discharged to hospice had significantly higher rates of PC than those who were discharged home or to rehabilitation (P < .0001). Conclusions: In our dataset, PC consultation rates varied by patient demographic, surgical status, discharging service, and practice setting. Further work is needed to identify the specific barriers to optimally utilizing specialty PC in this population.
Authors
Price, M; Howell, EP; Dalton, T; Ramirez, L; Howell, C; Williamson, T; Fecci, PE; Anders, CK; Check, DK; Kamal, AH; Goodwin, CR
MLA Citation
Price, Meghan, et al. “Inpatient palliative care utilization for patients with brain metastases.Neurooncol Pract, vol. 8, no. 4, Aug. 2021, pp. 441–50. Pubmed, doi:10.1093/nop/npab016.
URI
https://scholars.duke.edu/individual/pub1488917
PMID
34277022
Source
pubmed
Published In
Neuro Oncology Practice
Volume
8
Published Date
Start Page
441
End Page
450
DOI
10.1093/nop/npab016

Research Areas:

Blood-Brain Barrier
Brain metastasis
Cancer
Glioma
Glioma, Subependymal
Immunotherapy
Immunotherapy, Active
T cells
T cells--Effect of drugs on
T cells--Receptors
Translational Medical Research