Enrico Lugli, Principial Investigator, Laboratory of Translational Immunology at Humanitas Research Hospital, shared on LinkedIn:
“New paper from the lab!
What is the complexity of tumor-infiltrating regulatory T cells (Tregs) across human cancers?
Excited to share our latest work just published in Nature Communications!
In our new study, ‘Molecular heterogeneity and clonal origin of CCR8+ effector regulatory T cells in human cancer‘ by Julian Swatler and Simone Puccio at Humanitas Research, we dive deep into the complex landscape of Tregs across multiple epithelial cancers.
While CCR8+ effector Tregs are key drivers of immunosuppression in the tumor microenvironment and prime targets for novel immunotherapies, understanding their origins and internal diversity has remained a challenge.
Key Highlights of our Study:
- Core Intratumoral Signature: By combining single-cell RNA-sequencing datasets and spectral flow cytometry across 9 epithelial cancers, we identified a robust core signature of 88 genes consistently upregulated in tumor Tregs.
- Four Distinct Treg Subsets: We mapped out 4 major Treg subsets (CCR7+ quiescent, CCR8+ effector, CD161+, and intermediate), each characterized by unique tissue distributions, functions, and molecular drivers.
- Clonal Dynamics and Origins: Using single-cell TCR sequencing, we uncovered that protumoral CCR8+ effector Tregs show minimal clonal overlap with other intratumoral Treg subsets, rather they share clonal relationships with Tregs in tumor-draining lymph nodes and, at a lesser extent, with conventional T cells within the tumor.
This study offers a comprehensive resource to help guide the development and fine-tuning of next-generation CCR8-targeted cancer immunotherapies.
A huge thank you to all co-authors, collaborators, and AIRC – Foundation for Cancer Research NGO, Cancer Research Institute (CRI) and Bristol Myers Squibb who made this possible!
The study is particularly important because it inspired a translational clinical trial of Treg depletion in metastatic solid tumors soon to be activated at Humanitas Research Hospital in collaboration with Matteo Simonelli.
Title: Molecular heterogeneity and clonal origin of CCR8+ effector regulatory T cells in human cancer
Authors: Julian Swatler, Simone Puccio, Emanuele Voulaz, Giuseppe Marulli, Matthew Wheeler, Sharmila Sambanthamoorthy, Eloise Scamardella, Simona Feno, Sabina Testa, Chiara Camisaschi, Valentina Errico, Matteo Simonelli, Agnese Losurdo, Emilia Maria Cristina Mazza, Enrico Lugli
Other articles about Tregs on OncoDaily.