­čçČ­čçž Immunological mechanisms of resistance to CDK4/6 inhibitors in HR+ breast cancer » Luxembourg Institute of Health
Starseite ┬╗ Veranstaltungen ┬╗ ­čçČ­čçž Immunological mechanisms of resistance to CDK4/6 inhibitors in HR+ breast cancer

­čçČ­čçž Immunological mechanisms of resistance to CDK4/6 inhibitors in HR+ breast cancer

04/04/2023 11:30 an 14:00
  • Lecture Series Cancer Research

Speaker

Dr Lorenzo
Galluzzi

Principal Investigator – Weill Cornell Medical College

Abstract

While CDK4/6 inhibitors have been successfully implemented into the clinical management of advanced/metastatic HR+HER2- breast cancer, the majority of these patients ultimately progress and succumb to their disease, calling for the identification of clinically actionable resistance mechanisms.

Here, we harnessed an immunocompetent model of HR+HER2- breast cancer with unique translational features to mechanistically delineate a novel radiotherapy-preventable, CCL2-depedent pathway leading to the recruitment of hypoxia-sensitive, IL17A-secreting ╬│╬┤ T cells to the tumor microenvironment upon CDK4/6 inhibition, culminating with the repolarization of tumor-associated macrophages (TAMs) towards an immunosuppressive, CX3CR1+ phenotype. Consistent with mouse data, genetic signatures of IL17A signaling or ╬│╬┤ T cell infiltration, as well as the intratumoral levels of ╬│╬┤ T cells or CX3CR1+ TAMs, were associated with reduced disease specific survival or advanced tumor grade in two independent cohorts of patients with HR+HER2- breast cancer.

Similarly, high levels of circulating ╬│╬┤ T cells at baseline were negatively linked to progression-free survival in two series of patients with HR+HER2- breast cancer receiving CDK4/6 inhibitors, as were plasma CCL2 levels. Moreover, intratumoral ╬│╬┤ T cells were increased in biopsies from patients with HR+HER2- breast cancer relapsing on CDK4/6 inhibitors (as compared to baseline biopsies). Finally, CX3CR1+ TAMs had negative prognostic impact in patients with resectable HR+HER2- breast cancer from a clinical trial testing neoadjuvant PD-1 blockage followed by stereotactic body radiotherapy.

Taken together, these findings suggest that ╬│╬┤ T cells and CX3CR1+ TAMs may support clinical resistance to CDK4/6 inhibitors in at least some patients with HR+HER2- breast cancer.


Responsible Scientists
Dr Bassam
Janji
Dr Cl├ęment
Thomas

LOCATION

LIH Edison Building
Room: Pasteur/Curie
1A-B, rue Thomas Edison, Strassen L-1445 Luxembourg

LECTURE: 11:30am – 14:00pm

Please note that registration is mandatory by sending an email to siu-thinh.ho@lih.lu

Supported by:

Teilen auf

Datenschutz

Lesen Sie mehr ├╝ber den „Datenschutzhinweis: Verarbeitung personenbezogener Daten im Rahmen der Organisation von Veranstaltungen“.

Anstehende Veranstaltungen

Spenden