1050P - Independent of calendric age, T cells are phenotypically less senescent in successfully ICI-treated cancer patients that developed irAE

Background

Aging is a multifaceted biologic process rendering individuals more susceptible to infections, autoimmunity, degenerative diseases, and cancer. Biologic and calendric age are not strictly linked. On a cellular level, senescence is defined as a state of stable cell cycle arrest, in which cells become resistant to growth-promoting stimuli but stay metabolically active – exerting autocrine, paracrine and endocrine effects. Immune-senescence, in particular, is characterized by altered function of both innate and adaptive immune cells. How immune-senescence relates to the burden of immune-related adverse events (irAEs) in cancer patients (pts) treated with immune checkpoint inhibitors (ICI) remains ill-understood.

Methods

Here we report peripheral blood phenotyping-data (mass cytometry-based) from pts with metastatic solid tumours in stable remission after ICI. The cohort was divided into patients without irAE, or irAEs that had resulted in any of the following: i) systemic immunosuppression for >7 days, ii) hospitalisation, iii) discontinuation/interruption for >6 months. Healthy blood donors served as a control.

Results

Peripheral blood mononuclear cells (PBMCs) of 20 pts were analyzed. 11 pts were >70 years old (age range 71-84), and 13 pts had experienced irAEs. Independent of calendric age, pts with irAEs had (in absolute and relative terms) more naïve CD4+ and CD8+ T cells and less EM and TEMRA CD4+ and CD8+ T cells. High-resolution phenotyping further revealed irAE-pts having smaller CD4+ and CD8+ CD27-/CD28- T cell compartments, and cells in these compartments were expressing less CD57, CD244 and KLRG1 (all senescence markers). Lastly, expression of KLRG1 on naïve CD4+ T cells among pts with irAE was lower than in non-irAE counterparts.

Conclusions

In this discovery cohort, PBMCs from pts that developed irAEs were phenotypically younger than those that did not. Cause-consequence and the predictive value of these biologic signatures will now be tested prospectively.

Clinical trial identification

Editorial acknowledgement

Legal entity responsible for the study

The authors.

Funding

SNSF.

Disclosure

All authors have declared no conflicts of interest.