624P - Pan-cancer single-cell isoform atlas: Unraveling isoform dynamics in cancer immunotherapy

Background

Most cancer immunotherapy research focuses on gene-level expression, often bypassing the key role of alternative splicing in producing various isoform transcripts. Alternative splicing contributes significantly to tumor heterogeneity, progression, and therapy response^1-3. Understanding these dynamics is paramount for advancing personalized treatment strategies.

Methods

1. Data Integration - Integrated multi-omics data from diverse tumor types. - Focused on immune cells within the tumor microenvironment. 2. Sample collection - Gathered data from both pre- and post-immunotherapy treated patients. - Included clinical response details for comprehensive insights. 3. Isoform analysis - Constructed a single-cell isoform atlas capturing the landscape of alternative splicing events and isoform expression profiles across a vast array of cancers. - Investigated patterns of isoform diversity/plasticity: - Within and between different cancer types. - Between pre- and post-treatment scenarios. - Among responders vs. non-responders.

Results

Pan-cancer isoform signatures - For each cancer type and at the pan-cancer level, the isoform patterns of immune cell types linked with oncogenic processes between (i) healthy and cancer; (ii) pre- and post-treatment; (iii) immunotherapy responders and non-responders.

Conclusions

Our pan-cancer single-cell isoform atlas offers a groundbreaking perspective on isoform dynamics in cancer immune environment, enriching our comprehension of tumor intricacies and bolstering efforts toward precision oncology for individualized patient care.

References: 1. Climente-González, H., Porta-Pardo, E., Godzik, A. & Eyras, E. The Functional Impact of Alternative Splicing in Cancer. Cell Reports 20, 2215-2226 (2017). https://doi.org:https://doi.org/10.1016/j.celrep.2017.08.012.

2. Zhang, Y., Qian, J., Gu, C. & Yang, Y. Alternative splicing and cancer: a systematic review. Signal Transduction and Targeted Therapy 6, 78 (2021). https://doi.org:10.1038/s41392-021-00486-7

3. Bonnal, S. C., López-Oreja, I. & Valcárcel, J. Roles and mechanisms of alternative splicing in cancer - implications for care. Nature Reviews Clinical Oncology 17, 457-474 (2020). https://doi.org:10.1038/s41571-020-0350-x

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

L. Pan.

Funding

Has not received any funding.

Disclosure

The author has declared no conflicts of interest.