42P - TCCIA: A Comprehensive Resource for Exploring CircRNA in Cancer Immunotherapy

Background

Immunotherapies targeting immune checkpoints have gained increasing attention in cancer treatment, emphasizing the need for predictive biomarkers. Circular RNAs have emerged as critical regulators of tumor immunity, particularly in the PD-(L)1 pathway, and have shown potential in predicting the efficacy of immunotherapies. Therefore, the development of a comprehensive resource that integrates circRNA profiles, immunotherapy response data, and clinical benefits is crucial for advancing our understanding of circRNA-mediated tumor-immune interactions and developing effective immunotherapy biomarkers.

Methods

To address these gaps, we constructed the Cancer CircRNA Immunome Atlas (TCCIA), the first database that combines circRNA profiles, immunotherapy response data, and clinical outcomes across multi-cancer types. The construction of TCCIA involved applying standardized preprocessing to the raw sequencing FASTQ files, characterizing circRNA profiles using CIRCexplorer2, analyzing tumor immunophenotypes through IOBR, and compiling immunotherapy response data from diverse cohorts treated with ICBs.

Results

TCCIA encompasses over 3,700 clinical samples obtained from 18 cohorts treated with ICBs, including PD-1/PD-L1 and CTLA-4 inhibitors, along with other treatment modalities. The database provides researchers and clinicians with a cloud-based platform that enables interactive exploration of circRNA data in the context of ICB. The platform offers a range of analytical tools, including visualization of circRNA abundance and correlation, association analysis between circRNAs and clinical variables, assessment of the tumor immune microenvironment, exploration of tumor molecular signatures, evaluation of treatment response or prognosis, and identification of altered circRNAs in immunotherapy-sensitive and resistant tumors. To illustrate the utility, we performed a re-analysis on a melanoma cohort with TCCIA and found that an isoform of circTMTC3 played a significant role in predicting unfavorable survival outcomes and treatment nonresponse.

Conclusions

TCCIA represents a significant advancement over existing resources, providing a comprehensive platform to investigate the role of circRNAs in immune oncology.

Legal entity responsible for the study

The authors.

Funding

Has not received any funding.

Disclosure

All authors have declared no conflicts of interest.