Editor’s Note: In the field of immunotherapy for colorectal cancer (CRC), ADAR1, an essential RNA-editing enzyme, has gained significant attention in recent years. At the 2024 ESMO Asia Congress, Dr. Da Kang from Dr. Zhizhong Pan’s team at the Sun Yat-sen University Cancer Center presented their latest findings on ADAR1 expression in T cells and its impact on immunotherapy resistance in CRC (Abstract No. 95P). Digestive Oncology Frontier interviewed Dr. Da Kang at the conference to delve deeper into this groundbreaking research.

• Dr. Da Kang: In our earlier collaborative studies, we observed that ADAR1 expression increases in solid tumors resistant to immunotherapy. To explore its clinical significance in colorectal cancer, we initiated this research. As a critical RNA epigenetic modifier, ADAR1 edits double-stranded RNA (dsRNA), disrupting the MDA5-MAVS downstream pathway and inhibiting interferon (IFN) release, thereby dampening the inflammatory response. Recent studies have reported the role of ADAR1 in tumor immunotherapy, but our team focused specifically on its implications in CRC to complement existing findings.

Our research revealed that T cells in colorectal tumors are a primary source of ADAR1, which promotes T cell exhaustion and potentially mediates immunotherapy resistance. Previous studies mainly targeted tumor cells or relied on bulk tissue sequencing, with limited focus on the immune microenvironment. By analyzing full-length single-cell transcriptomic data, we mapped the RNA editing landscape in CRC and confirmed that ADAR1 expression in T cells impacts the efficacy of immune checkpoint inhibitors (ICIs). This discovery offers a fresh perspective on the mechanisms driving immunotherapy resistance.

In our study, non-PCR (non-pathologic complete response) patients exhibited higher T cell infiltration and ADAR1 expression. This suggests that the immune microenvironment’s “hot” or “cold” nature should be assessed by both the quantity and quality of T cells, enabling a more comprehensive evaluation. Future research will focus on combining ADAR1-targeted therapy with immunotherapy to reverse T cell exhaustion and potentially improve survival outcomes for these patients.

95P – ADAR1 of T Cells Rather Than Epitheliums Contributes the Bulk Expression and Induces Immune Exhaustion in Colorectal Cancer

About the Authors

Dr. Zhizhong Pan

• MD, PhD, Distinguished Professor, Chief Colorectal Surgeon
• Chief Expert in Colorectal Surgery at Sun Yat-sen University Cancer Center
• Senior Fellow, American College of Surgeons (FACS)
• Executive Chairman, China MDT Alliance for Colorectal Cancer
• Director, Laparoscopic Surgery Training Base, Chinese Medical Doctor Association
• Vice Chair, Tumor Metastasis Committee, Chinese Medical Doctor Association
• Vice Chair, Comprehensive Colorectal Cancer Treatment Committee, Chinese Medical Doctor Association
• Vice Chair, Digestive Oncology Committee, China International Exchange and Promotive Association for Medical and Healthcare
• Principal Investigator for 3 National Projects and 2 Provincial Funds
• Published over 200 academic papers
• Recipient of the First Prize of the Chinese Medical Association Science and Technology Award and the First Prize of the Guangdong Provincial Science and Technology Progress Award

Professor Rongxin Zhang

• MD, PhD, Chief Physician, Master’s Supervisor
• Graduated from Sun Yat-sen University in 2012 with a PhD in Oncology
• Visiting Scholar at the University of Hong Kong (2011) and University of Pennsylvania (2018-2019)
• Research Focus: Comprehensive treatment of colorectal cancer, including neoadjuvant chemoradiotherapy, immunotherapy, and metastasis mechanisms
• Published over 10 papers in journals like Annals of Oncology, Clinical Cancer Research, Nature Cancer, and Nature Communications
• Principal Investigator for projects funded by the National Natural Science Foundation and Guangdong Provincial Natural Science Foundation

Dr. Da Kang

• PhD Candidate under Dr. Zhizhong Pan
• Focused on comprehensive treatment and immunotherapy mechanisms in colorectal cancer