Darrell Fan

Mr. Darrell Fan

orcid

Research Focus & Metrics

Academic Career Length

3Years (2024-Present)

(Calculated once Scilit publication data is synced: current year − year of first publication + 1)

Representative Publications

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27 February 2025 in Vaccines
Verified
Journal Article
Open access
PDF file
HTHsin-Fang Tu
Hsin-Fang Tu
JTJulia Tao
Julia Tao
MHMing Hung Hu
Ming Hung Hu
DFDarrell Fan
Darrell Fan
YTYa-Chea Tsai
Ya-Chea Tsai
CHChien-Fu Hung
Chien-Fu Hung
Background: Ly6C expression in naïve CD8+ T cells plays a crucial role in enhancing their effector activity, suggesting potential implications for cancer immunotherapy. This study investigates the functional impact of Ly6C expression on CD8+ T cells and explores albumin-conjugated IFNβ (Alb-IFNβ) as a strategy to modulate Ly6C expression and improve cancer vaccine efficacy. Methods: We analyzed the functional differences between Ly6C high-expressing (Ly6Chi) and Ly6C low-expressing (Ly6Clo) naïve CD8+ T cells in tumor suppression. To assess the role of type I interferon signaling, we administered Alb-IFNβ in C57BL/6J and IFNAR−/− mice and measured Ly6C expression in CD8+ T cells. The therapeutic potential of Alb-IFNβ was further evaluated in combination with a vaccinia virus encoding the HPV-16 E7 antigen (CRT-E7 vaccine) in a syngeneic TC-1 tumor model, assessing tumor growth, survival, and antigen-specific CD8+ T cell responses. Results: Naïve CD8+ T cells with elevated Ly6C expression exhibited enhanced tumor-suppressive capacity and required lower activation thresholds for effector function. Alb-IFNβ treatment selectively increased Ly6Chi naïve CD8+ T cells in C57BL/6J mice but not in IFNAR−/− mice, confirming type I interferon’s role in Ly6C regulation. Combining Alb-IFNβ pretreatment with the CRT-E7 vaccine significantly enhanced antigen-specific CD8+ T cell immunity, reducing tumor growth and prolonging survival in TC-1 tumor-bearing mice. Conclusions: Our findings suggest that Alb-IFNβ may enhance the antitumor activity of naïve CD8+ T cells by modulating Ly6C expression. Alb-IFNβ could potentially improve the efficacy of HPV vaccinia-based cancer vaccines, warranting further investigation as an adjuvant strategy in cancer immunotherapy.

23 August 2024 in Current Oncology
Verified
Journal Article
Open access
PDF file
TPThuy Phan
Thuy Phan
DFDarrell Fan
Darrell Fan
LMLaleh G Melstrom
Laleh G Melstrom
Pancreatic adenocarcinoma represents one of the most challenging malignancies to treat, with dismal survival rates despite advances in therapeutic modalities. Immunotherapy, particularly vaccines, has emerged as a promising strategy to harness the body’s immune system in combating this aggressive cancer. This abstract reviews the trials and tribulations encountered in the development of vaccines targeting pancreatic adenocarcinoma. Key challenges include the immunosuppressive tumor microenvironment, the heterogeneity of tumor antigens, and a limited understanding of immune evasion mechanisms employed by pancreatic cancer cells. Various vaccine platforms, including peptide-based, dendritic cell-based, and viral vector-based vaccines, have been explored in preclinical and clinical settings. However, translating promising results from preclinical models to clinical efficacy has proven elusive. In recent years, mRNA vaccines have emerged as a promising immunotherapeutic strategy in the fight against various cancers, including pancreatic adenocarcinoma. We will discuss the potential applications, opportunities, and challenges associated with mRNA vaccines in pancreatic cancer treatment.

17 April 2024 in Vaccines
Verified
Journal Article
Open access
PDF file
LLLing Lim
Ling Lim
MHMing Hung Hu
Ming Hung Hu
DFDarrell Fan
Darrell Fan
HTHsin-Fang Tu
Hsin-Fang Tu
YTYa-Chea Tsai
Ya-Chea Tsai
CHChien-Fu Hung
Chien-Fu Hung
Human papillomavirus (HPV) remains a global health concern because it contributes to the initiation of various HPV-associated cancers such as anal, cervical, oropharyngeal, penile, vaginal, and vulvar cancer. In HPV-associated cancers, oncogenesis begins with an HPV infection, which is linked to the activation of the Janus protein tyrosine kinase (JAK)/STAT signaling pathway. Various STAT signaling pathways, such as STAT3 activation, have been well documented for their tumorigenic role, yet the role of STAT1 in tumor formation remains unclear. In the current study, STAT1−/− mice were used to investigate the role of STAT1 in the tumorigenesis of a spontaneous HPV E6/E7-expressing oral tumor model. Subsequently, our candidate HPV DNA vaccine CRT/E7 was administered to determine whether the STAT1−/− host preserves a therapeutic-responsive tumor microenvironment. The results indicated that STAT1−/− induces robust tumorigenesis, yet a controlled tumor response was attained upon CRT/E7 vaccination. Characterizing this treatment effect, immunological analysis found a higher percentage of circulating CD4+ and CD8+ T cells and tumor-specific cytotoxic T cells. In addition, a reduction in exhaustive lymphocyte activity was observed. Further analysis of a whole-cell tumor challenge affirmed these findings, as spontaneous tumor growth was more rapid in STAT1−/− mice. In conclusion, STAT1 deletion accelerates tumorigenesis, but STAT1−/− mice maintains immunocompetency in CRT/E7 treatments.

11 April 2025 in Annals of Surgery
Verified
Journal Article
Closed access
KMKelly Mahuron
Kelly Mahuron
PEPatricia Esslin
Patricia Esslin
VSVirginia Sun
Virginia Sun
OOOluwatimilehin Okunowo
Oluwatimilehin Okunowo
DFDarrell Fan
Darrell Fan
LMLaleh G Melstrom
Laleh G Melstrom
Objective: To determine whether perioperative monitoring with nursing triage intervention is feasible and improves surgical outcomes and recovery. Background: There are increased demands for outpatient recovery after complex gastrointestinal oncologic surgery with simultaneous expectations of improving quality of life and expedited functional recovery. Telemonitoring is a proposed mechanism to achieve these goals. Methods: This prospective randomized controlled trial was conducted at a single institution from October 2021 to July 2023, and follow-up was completed in August 2023. Adult patients undergoing gastrointestinal oncologic surgery were randomized to either the telemonitoring intervention arm or the enhanced usual care control arm. Patient-generated health data (PGHD) and electronic patient-reported outcomes (ePROs) were assessed at discharge, 2 days, 7 days, 14 days, and 30 days postdischarge. The telemonitoring intervention arm additionally received nursing triage support when PGHD deviated from defined thresholds. Results: A total of 129 participants [median (IQR) age, 53 (47–65); 43% female] were randomized. Fifty (39%) lived >50 miles from the medical center. Overall attrition was 12%, and there were no differences in feasibility, retention, or acceptability between arms. Postoperative complications and readmission rates were similar between arms. The intervention arm reported significantly lower MD Anderson Symptom Inventory (MDASI) interference with activity and symptom severity scores at multiple time points compared with the control arm ( P <0.05). Conclusions: This trial demonstrates that perioperative telemonitoring is feasible and acceptable. Improved ePROs in the intervention arm suggests that nursing triage intervention may help augment postoperative recovery.