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:

Preclinical Modeling of Surgery and Steroid Therapy for Glioblastoma Reveals Changes in Immunophenotype that are Associated with Tumor Growth and Outcome.

PURPOSE: Glioblastoma (GBM) immunotherapy clinical trials are generally initiated after standard-of-care treatment-including surgical resection, perioperative high-dose steroid therapy, chemotherapy, and radiation treatment-has either begun or failed. However, the impact of these interventions on the antitumoral immune response is not well studied. While discoveries regarding the impact of chemotherapy and radiation on immune response have been made and translated into clinical trial design, the impact of surgical resection and steroids on the antitumor immune response has yet to be determined. EXPERIMENTAL DESIGN: We developed a murine model integrating tumor resection and steroid treatment and used flow cytometry to analyze systemic and local immune changes. These mouse model findings were validated in a cohort of 95 patients with primary GBM. RESULTS: Using our murine resection model, we observed a systemic reduction in lymphocytes corresponding to increased tumor volume and decreased circulating lymphocytes that was masked by dexamethasone treatment. The reduction in circulating T cells was due to reduced CCR7 expression, resulting in T-cell sequestration in lymphoid organs and the bone marrow. We confirmed these findings in a cohort of patients with primary GBM and found that prior to steroid treatment, circulating lymphocytes inversely correlated with tumor volume. Finally, we demonstrated that peripheral lymphocyte content varies with progression-free survival and overall survival, independent of tumor volume, steroid use, or molecular profiles. CONCLUSIONS: These data reveal that prior to intervention, increased tumor volume corresponds with reduced systemic immune function and that peripheral lymphocyte counts are prognostic when steroid treatment is taken into account.
Authors
Otvos, B; Alban, TJ; Grabowski, MM; Bayik, D; Mulkearns-Hubert, EE; Radivoyevitch, T; Rabljenovic, A; Johnson, S; Androjna, C; Mohammadi, AM; Barnett, GH; Ahluwalia, MS; Vogelbaum, MA; Fecci, PE; Lathia, JD
MLA Citation
Otvos, Balint, et al. “Preclinical Modeling of Surgery and Steroid Therapy for Glioblastoma Reveals Changes in Immunophenotype that are Associated with Tumor Growth and Outcome.Clin Cancer Res, vol. 27, no. 7, Apr. 2021, pp. 2038–49. Pubmed, doi:10.1158/1078-0432.CCR-20-3262.
URI
https://scholars.duke.edu/individual/pub1481236
PMID
33542075
Source
pubmed
Published In
Clinical Cancer Research
Volume
27
Published Date
Start Page
2038
End Page
2049
DOI
10.1158/1078-0432.CCR-20-3262

RADIOGRAPHIC CHARACTERISTICS AND STEROID USAGE IN LASER INTERSTITIAL THERMAL THERAPY VERSUS MEDICAL MANAGEMENT FOR BIOPSY-PROVEN RADIATION NECROSIS AFTER STEREOTACTIC RADIOSURGERY OF BRAIN METASTASES

Authors
Srinivasan, E; Sankey, E; Grabowski, M; Griffin, A; Howell, E; Otvos, B; Tsvankin, V; Atik, A; Joshi, K; Barnett, G; Fecci, P; Mohammadi, A
URI
https://scholars.duke.edu/individual/pub1467837
Source
wos-lite
Published In
Neuro Oncology
Volume
22
Published Date
Start Page
116
End Page
117

Unique challenges for glioblastoma immunotherapy-discussions across neuro-oncology and non-neuro-oncology experts in cancer immunology. Meeting Report from the 2019 SNO Immuno-Oncology Think Tank.

Cancer immunotherapy has made remarkable advances with over 50 separate Food and Drug Administration (FDA) approvals as first- or second-line indications since 2015. These include immune checkpoint blocking antibodies, chimeric antigen receptor-transduced T cells, and bispecific T-cell-engaging antibodies. While multiple cancer types now benefit from these immunotherapies, notable exceptions thus far include brain tumors, such as glioblastoma. As such, it seems critical to gain a better understanding of unique mechanistic challenges underlying the resistance of malignant gliomas to immunotherapy, as well as to acquire insights into the development of future strategies. An Immuno-Oncology Think Tank Meeting was held during the 2019 Annual Society for Neuro-Oncology Scientific Conference. Discussants in the fields of neuro-oncology, neurosurgery, neuro-imaging, medical oncology, and cancer immunology participated in the meeting. Sessions focused on topics such as the tumor microenvironment, myeloid cells, T-cell dysfunction, cellular engineering, and translational aspects that are critical and unique challenges inherent with primary brain tumors. In this review, we summarize the discussions and the key messages from the meeting, which may potentially serve as a basis for advancing the field of immune neuro-oncology in a collaborative manner.
Authors
Chuntova, P; Chow, F; Watchmaker, PB; Galvez, M; Heimberger, AB; Newell, EW; Diaz, A; DePinho, RA; Li, MO; Wherry, EJ; Mitchell, D; Terabe, M; Wainwright, DA; Berzofsky, JA; Herold-Mende, C; Heath, JR; Lim, M; Margolin, KA; Chiocca, EA; Kasahara, N; Ellingson, BM; Brown, CE; Chen, Y; Fecci, PE; Reardon, DA; Dunn, GP; Liau, LM; Costello, JF; Wick, W; Cloughesy, T; Timmer, WC; Wen, PY; Prins, RM; Platten, M; Okada, H
MLA Citation
URI
https://scholars.duke.edu/individual/pub1470066
PMID
33367885
Source
pubmed
Published In
Neuro Oncol
Volume
23
Published Date
Start Page
356
End Page
375
DOI
10.1093/neuonc/noaa277

Immuno-synergy? Neoantigen vaccines and checkpoint blockade in glioblastoma.

Authors
Woroniecka, K; Fecci, PE
MLA Citation
Woroniecka, Karolina, and Peter E. Fecci. “Immuno-synergy? Neoantigen vaccines and checkpoint blockade in glioblastoma.Neuro Oncol, vol. 22, no. 9, Sept. 2020, pp. 1233–34. Pubmed, doi:10.1093/neuonc/noaa170.
URI
https://scholars.duke.edu/individual/pub1463585
PMID
32691060
Source
pubmed
Published In
Neuro Oncol
Volume
22
Published Date
Start Page
1233
End Page
1234
DOI
10.1093/neuonc/noaa170

Salting the Soil: Targeting the Microenvironment of Brain Metastases.

Paget's "seed and soil" hypothesis of metastatic spread has acted as a foundation of the field for over a century, with continued evolution as mechanisms of the process have been elucidated. The central nervous system (CNS) presents a unique soil through this lens, relatively isolated from peripheral circulation and immune surveillance with distinct cellular and structural composition. Research in primary and metastatic brain tumors has demonstrated that this tumor microenvironment (TME) plays an essential role in the growth of CNS tumors. In each case, the cancerous cells develop complex and bidirectional relationships that reorganize the local TME and reprogram the CNS cells, including endothelial cells, pericytes, astrocytes, microglia, infiltrating monocytes, and lymphocytes. These interactions create a structurally and immunologically permissive TME with malignant processes promoting positive feedback loops and systemic consequences. Strategies to interrupt interactions with the native CNS components, on "salting the soil," to create an inhospitable environment are promising in the preclinical setting. This review aims to examine the general and specific pathways thus far investigated in brain metastases and related work in glioma to identify targetable mechanisms that may have general application across the spectrum of intracranial tumors.
Authors
MLA Citation
Srinivasan, Ethan S., et al. “Salting the Soil: Targeting the Microenvironment of Brain Metastases.Mol Cancer Ther, vol. 20, no. 3, Mar. 2021, pp. 455–66. Pubmed, doi:10.1158/1535-7163.MCT-20-0579.
URI
https://scholars.duke.edu/individual/pub1471070
PMID
33402399
Source
pubmed
Published In
Mol Cancer Ther
Volume
20
Published Date
Start Page
455
End Page
466
DOI
10.1158/1535-7163.MCT-20-0579

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