Publications by authors named "Olutosin Owoyemi"

6 Publications

  • Page 1 of 1

Supraphysiologic Testosterone Induces Ferroptosis and Activates Immune Pathways through Nucleophagy in Prostate Cancer.

Cancer Res 2021 12 13;81(23):5948-5962. Epub 2021 Oct 13.

The Sidney Kimmel Comprehensive Cancer Center, Johns Hopkins University School of Medicine, Baltimore, Maryland.

The discovery that androgens play an important role in the progression of prostate cancer led to the development of androgen deprivation therapy (ADT) as a first line of treatment. However, paradoxical growth inhibition has been observed in a subset of prostate cancer upon administration of supraphysiologic levels of testosterone (SupraT), both experimentally and clinically. Here we report that SupraT activates cytoplasmic nucleic acid sensors and induces growth inhibition of SupraT-sensitive prostate cancer cells. This was initiated by the induction of two parallel autophagy-mediated processes, namely, ferritinophagy and nucleophagy. Consequently, autophagosomal DNA activated nucleic acid sensors converge on NFκB to drive immune signaling pathways. Chemokines and cytokines secreted by the tumor cells in response to SupraT resulted in increased migration of cytotoxic immune cells to tumor beds in xenograft models and patient tumors. Collectively, these findings indicate that SupraT may inhibit a subset of prostate cancer by activating nucleic acid sensors and downstream immune signaling. SIGNIFICANCE: This study demonstrates that supraphysiologic testosterone induces two parallel autophagy-mediated processes, ferritinophagy and nucleophagy, which then activate nucleic acid sensors to drive immune signaling pathways in prostate cancer.
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http://dx.doi.org/10.1158/0008-5472.CAN-20-3607DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8639619PMC
December 2021

SARS-CoV-2 Seropositivity and Seroconversion in Patients Undergoing Active Cancer-Directed Therapy.

JCO Oncol Pract 2021 12 16;17(12):e1879-e1886. Epub 2021 Jun 16.

Department of Genetics, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, PA.

Purpose: Multiple studies have demonstrated the negative impact of cancer care delays during the COVID-19 pandemic, and transmission mitigation techniques are imperative for continued cancer care delivery. We aimed to gauge the effectiveness of these measures at the University of Pennsylvania.

Methods: We conducted a longitudinal study of SARS-CoV-2 antibody seropositivity and seroconversion in patients presenting to infusion centers for cancer-directed therapy between May 21, 2020, and October 8, 2020. Participants completed questionnaires and had up to five serial blood collections.

Results: Of 124 enrolled patients, only two (1.6%) had detectable SARS-CoV-2 antibodies on initial blood draw, and no initially seronegative patients developed newly detectable antibodies on subsequent blood draw(s), corresponding to a seroconversion rate of 0% (95% CI, 0.0 TO 4.1%) over 14.8 person-years of follow up, with a median of 13 health care visits per patient.

Conclusion: These results suggest that patients with cancer receiving in-person care at a facility with aggressive mitigation efforts have an extremely low likelihood of COVID-19 infection.
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http://dx.doi.org/10.1200/OP.21.00113DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8677966PMC
December 2021

CD8 T cells contribute to survival in patients with COVID-19 and hematologic cancer.

Nat Med 2021 07 20;27(7):1280-1289. Epub 2021 May 20.

Abramson Cancer Center, University of Pennsylvania, Philadelphia, PA, USA.

Patients with cancer have high mortality from coronavirus disease 2019 (COVID-19), and the immune parameters that dictate clinical outcomes remain unknown. In a cohort of 100 patients with cancer who were hospitalized for COVID-19, patients with hematologic cancer had higher mortality relative to patients with solid cancer. In two additional cohorts, flow cytometric and serologic analyses demonstrated that patients with solid cancer and patients without cancer had a similar immune phenotype during acute COVID-19, whereas patients with hematologic cancer had impairment of B cells and severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-specific antibody responses. Despite the impaired humoral immunity and high mortality in patients with hematologic cancer who also have COVID-19, those with a greater number of CD8 T cells had improved survival, including those treated with anti-CD20 therapy. Furthermore, 77% of patients with hematologic cancer had detectable SARS-CoV-2-specific T cell responses. Thus, CD8 T cells might influence recovery from COVID-19 when humoral immunity is deficient. These observations suggest that CD8 T cell responses to vaccination might provide protection in patients with hematologic cancer even in the setting of limited humoral responses.
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http://dx.doi.org/10.1038/s41591-021-01386-7DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8291091PMC
July 2021

Underrepresentation in Oncology: Identifying and Addressing Structural Barriers.

Oncologist 2021 08 19;26(8):630-634. Epub 2021 Apr 19.

Perelman School of Medicine, The University of Pennsylvania, Philadelphia, Pennsylvania, USA.

Underrepresentation of minority groups in the oncology physician workforce is a pressing issue that may contribute to disparities in cancer research, clinical care, and patient outcomes. To address this, we highlight the role of medical culture and institutions in perpetuating a range of barriers that lead to the persistent underrepresentation of minority medical trainees and physicians. These barriers include an exclusionary medical culture, bias in measures of merit, financial barriers to medical subspecialty training, underrecognition of achievement, and poor representation and satisfaction among underrepresented faculty. Furthermore, we suggest a more intentional approach to diversity that values both recruitment of underrepresented undergraduates and early medical students and retention of internal medicine trainees, hematology-oncology fellows, and faculty. To counteract deeply embedded structural racism that hampers diversity efforts, this multifaceted approach will require cultural transformation of our medical institutions at all levels, including increased institutional transparency, mandatory evidence-based bias training, acknowledgment of varied achievements, changes in recruitment practices, and reinvigoration of pipeline development programs with a focus on financial support. Taken in combination, programs should recognize the scope of deterrents to representation and develop program-specific, longitudinal interventions to promote more successful diversity initiatives within the field of oncology. IMPLICATIONS FOR PRACTICE: The medical profession recognizes the value of physician workforce diversity in improving the quality of both medical education and patient care. In return, medical schools and training programs invest in recruitment programs focused on candidates who are underrepresented in medicine. In the field of oncology, where stark racial and ethnic disparities in care and health outcomes are well-defined, measures of minority physician representation remain especially stagnant. This study clearly defines the barriers that limit the effectiveness of such programs and provides recommendations to achieve the necessary workforce diversity in oncology.
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http://dx.doi.org/10.1002/onco.13771DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8342590PMC
August 2021

CD8 T cells compensate for impaired humoral immunity in COVID-19 patients with hematologic cancer.

Res Sq 2021 Feb 2. Epub 2021 Feb 2.

Cancer patients have increased morbidity and mortality from Coronavirus Disease 2019 (COVID-19), but the underlying immune mechanisms are unknown. In a cohort of 100 cancer patients hospitalized for COVID-19 at the University of Pennsylvania Health System, we found that patients with hematologic cancers had a significantly higher mortality relative to patients with solid cancers after accounting for confounders including ECOG performance status and active cancer status. We performed flow cytometric and serologic analyses of 106 cancer patients and 113 non-cancer controls from two additional cohorts at Penn and Memorial Sloan Kettering Cancer Center. Patients with solid cancers exhibited an immune phenotype similar to non-cancer patients during acute COVID-19 whereas patients with hematologic cancers had significant impairment of B cells and SARS-CoV-2-specific antibody responses. High dimensional analysis of flow cytometric data revealed 5 distinct immune phenotypes. An immune phenotype characterized by CD8 T cell depletion was associated with a high viral load and the highest mortality of 71%, among all cancer patients. In contrast, despite impaired B cell responses, patients with hematologic cancers and preserved CD8 T cells had a lower viral load and mortality. These data highlight the importance of CD8 T cells in acute COVID-19, particularly in the setting of impaired humoral immunity. Further, depletion of B cells with anti-CD20 therapy resulted in almost complete abrogation of SARS-CoV-2-specific IgG and IgM antibodies, but was not associated with increased mortality compared to other hematologic cancers, when adequate CD8 T cells were present. Finally, higher CD8 T cell counts were associated with improved overall survival in patients with hematologic cancers. Thus, CD8 T cells likely compensate for deficient humoral immunity and influence clinical recovery of COVID-19. These observations have important implications for cancer and COVID-19-directed treatments, immunosuppressive therapies, and for understanding the role of B and T cells in acute COVID-19.
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http://dx.doi.org/10.21203/rs.3.rs-162289/v1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7872363PMC
February 2021

SARS-CoV-2 seropositivity and seroconversion in patients undergoing active cancer-directed therapy.

medRxiv 2021 Jan 16. Epub 2021 Jan 16.

Multiple studies have demonstrated the negative impact of cancer care delays during the COVID-19 pandemic, and transmission mitigation techniques are imperative for continued cancer care delivery. To gauge the effectiveness of these measures at the University of Pennsylvania, we conducted a longitudinal study of SARS-CoV-2 antibody seropositivity and seroconversion in patients presenting to infusion centers for cancer-directed therapy between 5/21/2020 and 10/8/2020. Participants completed questionnaires and had up to five serial blood collections. Of 124 enrolled patients, only two (1.6%) had detectable SARS-CoV-2 antibodies on initial blood draw, and no initially seronegative patients developed newly detectable antibodies on subsequent blood draw(s), corresponding to a seroconversion rate of 0% (95%CI 0.0-4.1%) over 14.8 person-years of follow up, with a median of 13 healthcare visits per patient. These results suggest that cancer patients receiving in-person care at a facility with aggressive mitigation efforts have an extremely low likelihood of COVID-19 infection.
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http://dx.doi.org/10.1101/2021.01.15.21249810DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7814843PMC
January 2021
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