Ipilimumab reshapes T cell memory subsets in melanoma patients with clinical response.
Therapy targeting CTLA-4 immune checkpoint provides increased survival in patients with advanced melanoma. However, immunotherapy is frequently associated with delayed and heterogeneous clinical responses and it is important to identify prognostic immunological correlates of clinical endpoints.



77 patients with stage III/IV melanoma were treated with ipilimumab alone every 3 weeks, during 9 weeks. Blood samples were collected at the baseline and before each dose for in depth immune monitoring.



The median follow-up was 28 mo with a median survival of 7 mo. Survival and clinical benefit were significantly improved when absolute lymphocyte count at the baseline was above 1 × 10(9)/L. Notably, ipilimumab had a global effect on memory T cells, with an early increase of central and effector subsets in patients with disease control. By contrast, percentages of stem cell memory T cells (TSCM) gradually decreased despite stable absolute counts and sustained proliferation, suggesting a process of differentiation. Higher proportions of eomes(+) and Ki-67(+) T cells were observed, with enhanced skin homing potential and induction of cytotoxic markers.



These results suggest that CTLA-4 blockade is able to reshape the memory subset with the potential involvement of Eomes and memory subsets including TSCM.
INSERM, UMR-1160, Institut Universitaire d'Hématologie, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France.
Joana
J
Felix
Université Paris Diderot, Sorbonne Paris Cité, Paris, France; AP-HP, Hôpital Saint-Louis, Service de Biostatistique et Informatique Médicale, Paris, France; INSERM, UMR 1153, Center de Recherche Epidémiologie et Statistique (CRESS), Paris, France.
Jérome
J
Lambert
INSERM, UMR-1160, Institut Universitaire d'Hématologie , Paris, France.
Marie
M
Roelens
Service de Dermatologie, Hôpital Xavier Bichat , AP-HP , Paris, France.
Eve
E
Maubec
INSERM, UMR-1160, Institut Universitaire d'Hématologie , Paris, France.
Hélène
H
Guermouche
Service de Dermatologie , AP-HP , Hôpital Saint Louis, Paris, France.
Cécile
C
Pages
Service de Dermatologie , AP-HP , Hôpital Saint Louis, Paris, France.
Irina
I
Sidina
INSERM, UMR-1160, Institut Universitaire d'Hématologie, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Laboratoire d'Immunologie-Histocompatibilité, AP-HP, Hôpital Saint Louis, Paris, France.
Debora J
DJ
Cordeiro
Laboratoire d'Immunologie-Histocompatibilité , AP-HP , Hôpital Saint Louis, Paris, France.
Guitta
G
Maki
Service de Dermatologie , AP-HP , Hôpital Saint Louis, Paris, France.
François
F
Chasset
INSERM, UMR 1153, Center de Recherche Epidémiologie et Statistique (CRESS), Paris, France; Centre d'Epidémiologie Clinique, Hôtel-Dieu, AP-HP, Paris, France; Université Paris Descartes, Sorbonne Paris Cité, Paris, France.
Raphaël
R
Porcher
Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Service de Dermatologie, AP-HP, Hôpital Saint Louis, Paris, France; INSERM, UMR-976, Hôpital Saint-Louis, Paris, France.
Martine
M
Bagot
INSERM, UMR-1160, Institut Universitaire d'Hématologie , Paris, France.
Anne
A
Caignard
INSERM, UMR-1160, Institut Universitaire d'Hématologie, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Laboratoire d'Immunologie-Histocompatibilité, AP-HP, Hôpital Saint Louis, Paris, France.
Antoine
A
Toubert
Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Service de Dermatologie, AP-HP, Hôpital Saint Louis, Paris, France; INSERM, UMR-976, Hôpital Saint-Louis, Paris, France.
Céleste
C
Lebbé
INSERM, UMR-1160, Institut Universitaire d'Hématologie, Paris, France; Université Paris Diderot, Sorbonne Paris Cité, Paris, France; Laboratoire d'Immunologie-Histocompatibilité, AP-HP, Hôpital Saint Louis, Paris, France.
Hélène
H
Moins-Teisserenc
CTLA-4; TSCM; immunotherapy; ipilimumab; melanoma; memory T cells