Publications by authors named "T M Wise-Draper"

45 Publications

Immune Checkpoint Inhibitors Regulate K Channel Activity in Cytotoxic T Lymphocytes of Head and Neck Cancer Patients.

Front Pharmacol 2021 27;12:742862. Epub 2021 Aug 27.

Department of Internal Medicine, Division of Nephrology, University of Cincinnati, Cincinnati, OH, United States.

Programmed death receptor-1 (PD-1) and its ligand (PD-L1) interaction negatively regulates T cell function in head and neck squamous cell carcinoma (HNSCC). Overexpression of PD-1 reduces intracellular Ca fluxes, and thereby T cell effector functions. In HNSCC patients, PD-1 blockade increases KCa3.1 and Kv1.3 activity along with Ca signaling and mobility in CD8 peripheral blood T cells (PBTs). The mechanism by which PD-L1/PD-1 interaction regulates ion channel function is not known. We investigated the effects of blocking PD-1 and PD-L1 on ion channel functions and intracellular Ca signaling in CD8 PBTs of HNSCC patients and healthy donors (HDs) using single-cell electrophysiology and live microscopy. Anti-PD-1 and anti-PD-L1 antibodies increase KCa3.1 and Kv1.3 function in CD8 PBTs of HNSCC patients. Anti-PD-1 treatment increases Ca fluxes in a subset of HSNCC patients. In CD8 PBTs of HDs, exposure to PD-L1 reduces KCa3.1 activity and Ca signaling, which were restored by anti-PD-1 treatment. The PD-L1-induced inhibition of KCa3.1 channels was rescued by the intracellular application of the PI3 kinase modulator phosphatidylinositol 3-phosphate (PI3P) in patch-clamp experiments. In HNSCC CD8 PBTs, anti-PD-1 treatment did not affect the expression of KCa3.1, Kv1.3, Ca release activated Ca (CRAC) channels, and markers of cell activation (CD69) and exhaustion (LAG-3 and TIM-3). Our data show that immune checkpoint blockade improves T cell function by increasing KCa3.1 and Kv1.3 channel activity in HNSCC patients.
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http://dx.doi.org/10.3389/fphar.2021.742862DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8429813PMC
August 2021

Adjuvant radiation and cetuximab improves local control in head and neck cutaneous squamous cell carcinoma: A phase II study.

Head Neck 2021 Aug 7. Epub 2021 Aug 7.

Department of Radiation Oncology, University of Cincinnati, Cincinnati, Ohio, USA.

Background: Cutaneous squamous cell carcinoma of the head/neck (CSCCHN) is common due to chronic sun exposure. As CSCCHN highly expresses EGFR, we prospectively studied postoperative concurrent cetuximab with radiotherapy for locally advanced CSCCHN (LA-CSCCHN).

Materials And Methods: Single-institutional phase II trial of LA-CSCCHN (NCT XXXX). Adjuvant radiation was given with concurrent cetuximab. Primary endpoint of 2-year LRC and secondary objectives of 2-year disease-free survival (DFS) and 2-year OS were assessed by Kaplan-Meier analysis.

Results: Twenty-four patients ages 47-88 (median 71 years) were treated from 2014 to 2017. Fourteen patients had T3/4 disease, 5 had N1 disease, and 7 were N2/3. At median follow-up of 42 months, median OS and DFS was not reached and 64 months. Two-year OS was 75%, 2-year DFS was 70.8%. LRC was 91.1% at 2 years. All grade 3 adverse events were related to skin toxicity (12.5% radiation-related dermatitis, 16.7% cetuximab-related rash).

Conclusions: LRC compares favorably to historical data examining postoperative radiation alone but requires further investigation.
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http://dx.doi.org/10.1002/hed.26835DOI Listing
August 2021

Human Papillomavirus and Survival of Sinonasal Squamous Cell Carcinoma Patients: A Systematic Review and Meta-Analysis.

Cancers (Basel) 2021 Jul 22;13(15). Epub 2021 Jul 22.

University of Cincinnati Cancer Center, Cincinnati, OH 45267, USA.

Human papillomavirus (HPV) is detectable in a subset of sinonasal squamous cell carcinoma (SNSCC), but the impact on patient outcomes is presently unclear due to a modest number of studies with limited statistical power. Therefore, we conducted a systematic review and meta-analysis to better clarify this relationship. A PubMed search was conducted to identify all studies reporting on overall (OS) or disease-free survival (DFS) for SNSCC by HPV status. Hazard ratios (HR) and corresponding 95% confidence intervals (CI) were extracted or, when not provided, indirectly estimated from each manuscript. Summary survival curves for 5-year OS and estimating survival probability by HPV status at pre-specified time intervals from study-specific Kaplan-Meier curves generated 2-year DFS. Log HRs and log CIs were combined across studies to generate summary estimates and a corresponding 95% CIs for OS and DFS. We identified ten unique studies reporting on OS and four for DFS. We observed a significant association between HPV and OS (summary HR = 0.51, 95% CI: 0.38-0.70) with relatively low heterogeneity between studies. These results indicate that HPV is a significant predictor of more favorable survival for SNSCC, and thus may be a useful biomarker for prognostication and, potentially, treatment modulation.
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http://dx.doi.org/10.3390/cancers13153677DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8345036PMC
July 2021

Managing Recurrent Metastatic Head and Neck Cancer.

Hematol Oncol Clin North Am 2021 Oct 2;35(5):1009-1020. Epub 2021 Jul 2.

Division of Hematology/Oncology, University of Cincinnati, 3125 Eden Avenue, Cincinnati, OH 45267-0562, USA. Electronic address:

Head and neck squamous cell carcinoma (HNSCC) treatment is often associated with high morbidity especially in the recurrent and/or metastatic (R/M) setting, limiting effective treatment options. Local disease control is important. Therefore, local therapies including reirradiation and salvage surgery, either alone or in combination with systemic treatment, may be used for selected patients with R/M HNSCC. Although chemotherapy and targeted agents have modest efficacy in HNSCC, the advent of immunotherapy has revolutionized the treatment paradigm of R/M HNSCC. Multiple trials have resulted in the past 5 years advocating for its use alone or in combination with chemotherapy.
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http://dx.doi.org/10.1016/j.hoc.2021.05.009DOI Listing
October 2021

Pre-treatment absolute lymphocyte count predicts for improved survival in human papillomavirus (HPV)-driven oropharyngeal squamous cell carcinoma.

Oral Oncol 2021 May 23;116:105245. Epub 2021 Apr 23.

University of Cincinnati, Department of Radiation Oncology, Cincinnati, OH, United States; Cincinnati VA Medical Center, Cincinnati, OH, United States. Electronic address:

Background: The prognostic value of pretreatment complete blood count (CBC) data, including absolute lymphocyte count (ALC) and the neutrophil-to-lymphocyte ratio (NLR), has been reported for many diseases with decreased ALC and increased absolute neutrophil count (ANC) and NLR values correlating with worse outcomes. There is minimal data relating these hematologic parameters to oropharyngeal squamous cell carcinoma (OPSCC) prognosis. This study evaluates the prognostic value of pretreatment CBC data in OPSCC on overall survival (OS) and progression-free survival (PFS) in relation to HPV status.

Methods: A single-institutional retrospective review of patients with pretreatment hematologic data who received radiation for OPSCC was performed. Univariate and multivariate (UVA/MVA) Cox proportional hazard regression analyses were performed to identify prognostic variables. Translational studies related outcomes to the degree of tumor-infiltrating lymphocytes (TILs) in histologic specimens.

Results: From 2007 to 2018, 201 patients were treated for OPSCC. Median follow-up was 40 months. 3-year OS was 86.2% in the HPV-positive cohort, 46.3% for HPV-negative. Median NLR was 3.04. NLR ≥ 3 was associated with worse PFS (HR 1.67, p = 0.044. In the subset of 158 HPV + patients, MVA revealed increasing ALC to be associated with improved OS (HR 0.53; p = 0.040) and PFS (HR = 0.48; p = 0.0075). On UVA, high-TIL infiltration at diagnosis was associated with improved OS.

Conclusion: In a cohort of HPV + OPSCC patients, increasing ALC is associated with improved OS and PFS. Our study is the first to identify pre-treatment ALC as an independent prognostic factor in HPV-associated OPSCC.
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http://dx.doi.org/10.1016/j.oraloncology.2021.105245DOI Listing
May 2021
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