The EACR’s Top 10 Cancer Research Publications is a regular summary of the most interesting and impactful recent papers in cancer research. It is curated by the Board of the European Association for Cancer Research (EACR).
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S. Valpione et al. Nature Cancer vol. 1,2 (2020): 210-221
Summary of the findings
Immunotherapy with cytotoxic T lymphocyte associated protein-4 (CTLA4) and programmed death-1 (PD1) immune-checkpoint blockade (ICB) is increasingly utilised to treat solid tumours both in the metastatic and the neoadjuvant/adjuvant setting. Unfortunately, most patients do not respond to these drugs and some experience significant toxicity without benefit. New strategies are therefore needed to identify which patients will benefit from these treatments and to improve the chance of response in the majority of patients. To advance knowledge of the response dynamics induced by ICB, we analysed T cell phenotypes and T cell receptor (TCR) repertoire evolution under the selective pressure of ICB. We identified a subset of circulating T cells that early during treatment identifies the patients with better outcomes, and we discovered cell-free DNA-based TCR signatures that can track effective responses. The immune-signatures we identified have all the advantages associated with minimally invasive liquid biopsies, can identify responders after the first cycle of therapy and shed a light onto T cell dynamics associated with effective immune-responses in patients receiving ICB drugs.
Future perspectives
Our results will allow development of new strategies to improve cancer care, by highlighting how TCR repertoires evolve during effective responses and by identifying the T cell subset that expands early during treatment. This will guide the design of new immune-biomarkers for future clinical development and has also contributed to our understanding of the mechanisms underlying effective immune-response induced by ICB drugs.
