Simon Pernot1,2, Magali Terme3, Nina Radosevic-Robin4, Florence Castan5, Cécile Badoual3,6, Elie Marcheteau3, Fréderique Penault-Llorca4, Olivier Bouche7, Jaafar Bennouna8, Eric Francois9, Francois Ghiringhelli10, Christelle De La Fouchardiere11, Emmanuelle Samalin12, Jean Baptiste Bachet13, Christophe Borg14, Valérie Boige15, Thibault Voron3, Trevor Stanbury16, Eric Tartour3, Sophie Gourgou5, David Malka15, Julien Taieb3,17. 1. Université de Paris, PARCC, INSERM, 75015, Paris, France. simon.pernot@aphp.fr. 2. Hôpital Européen Georges-Pompidou, APHP; Department of GI oncology, Université de Paris, Paris, France. simon.pernot@aphp.fr. 3. Université de Paris, PARCC, INSERM, 75015, Paris, France. 4. Department of Biopathology, Centre Jean Perrin and University Clermont Auvergne/INSERM U1240, Clermont-Ferrand, France. 5. Biometrics Unit, Institut du Cancer Montpellier-Val d'Aurelle, Université de Montpellier, Montpellier, France. 6. Department of Pathology, Université de Paris, Sorbonne Paris Cité, Paris, France. 7. CHU Robert Debré, Reims, France. 8. Institut de Cancérologie de l'Ouest-Site René Gauducheau, Saint Herblain, France. 9. Centre Antoine-Lacassagne, Nice, France. 10. Centre Georges-François Leclerc, Dijon, France. 11. Centre Léon Bérard, Lyon, France. 12. Institut du Cancer Montpellier-Val d'Aurelle, Université de Montpellier, Montpellier, France. 13. Pitié Salpétrière Hospital, Paris, France. 14. Medical Oncology Unit, CHU Minjoz, Besancon, France. 15. Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France. 16. UNICANCER, Paris, France. 17. Hôpital Européen Georges-Pompidou, APHP; Department of GI oncology, Université de Paris, Paris, France.
Abstract
BACKGROUND: The correlation between immune cells and the Lauren classification subtypes and their prognostic impact in advanced gastric cancer (AGC) are unknown. METHODS:Circulating natural killer (NK) cells, CD4+ and CD8+ T cells, regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) were quantified in peripheral blood mononuclear cells (PBMCs) from 67 patients with untreated AGC enrolled in the PRODIGE 17-ACCORD 20 trial. CD56+ cells (NK), CD8+, and FoxP3+ (Treg) tumor-infiltrating lymphocytes (TILs) were assessed in tumor samples. RESULTS:Circulating NK and Treg proportions were significantly lower in patients with diffuse/mixed-type AGC (n = 27) than those with intestinal type (n = 40; median 6.3% vs 11.5%; p = 0.02 and median 3.3% vs 5.2%; p = 0.03, respectively). Proportions of circulating MDSC, CD4+ and CD8+ T cells were not associated with one pathological type. Among tumor-infiltrating cells, CD8+ T cells, but not NK or FoxP3+ cells, were significantly lower in diffuse/mixed-type AGC (median 21 vs 59 cells/field; p = 0.009). Patients with high circulating NK cell counts (> 17%) had a better overall survival than those with < 17% (HR 0.40; 95% CI [0.15-1.06]; p = 0.04). Patients with high CD8+ TIL counts (> 31 cells/field) had significantly longer overall survival (HR 0.44; 95% CI [0.21-0.92]; p = 0.02). The prognostic value of CD8+ TILs was maintained after adjustment for confounding factors, including the Lauren classification (HR = 0.42; 95% CI [0.18-0.96]; p = 0.039). CONCLUSION: Diffuse/mixed-type AGC has lower rates of CD8+ TILs and circulating NK cells and Tregs than the intestinal type. This "cold tumor" phenotype may be associated with a worse outcome.
RCT Entities:
BACKGROUND: The correlation between immune cells and the Lauren classification subtypes and their prognostic impact in advanced gastric cancer (AGC) are unknown. METHODS: Circulating natural killer (NK) cells, CD4+ and CD8+ T cells, regulatory T cells (Tregs) and myeloid-derived suppressor cells (MDSCs) were quantified in peripheral blood mononuclear cells (PBMCs) from 67 patients with untreated AGC enrolled in the PRODIGE 17-ACCORD 20 trial. CD56+ cells (NK), CD8+, and FoxP3+ (Treg) tumor-infiltrating lymphocytes (TILs) were assessed in tumor samples. RESULTS: Circulating NK and Treg proportions were significantly lower in patients with diffuse/mixed-type AGC (n = 27) than those with intestinal type (n = 40; median 6.3% vs 11.5%; p = 0.02 and median 3.3% vs 5.2%; p = 0.03, respectively). Proportions of circulating MDSC, CD4+ and CD8+ T cells were not associated with one pathological type. Among tumor-infiltrating cells, CD8+ T cells, but not NK or FoxP3+ cells, were significantly lower in diffuse/mixed-type AGC (median 21 vs 59 cells/field; p = 0.009). Patients with high circulating NK cell counts (> 17%) had a better overall survival than those with < 17% (HR 0.40; 95% CI [0.15-1.06]; p = 0.04). Patients with high CD8+ TIL counts (> 31 cells/field) had significantly longer overall survival (HR 0.44; 95% CI [0.21-0.92]; p = 0.02). The prognostic value of CD8+ TILs was maintained after adjustment for confounding factors, including the Lauren classification (HR = 0.42; 95% CI [0.18-0.96]; p = 0.039). CONCLUSION: Diffuse/mixed-type AGC has lower rates of CD8+ TILs and circulating NK cells and Tregs than the intestinal type. This "cold tumor" phenotype may be associated with a worse outcome.
Entities:
Keywords:
Advanced gastric adenocarcinoma; Biomarker; CD8+ T lymphocytes; Natural killer cells; Regulatory T cells
Authors: S Ishigami; S Natsugoe; K Tokuda; A Nakajo; X Che; H Iwashige; K Aridome; S Hokita; T Aikou Journal: Cancer Date: 2000-02-01 Impact factor: 6.860
Authors: Eric Tartour; H Pere; B Maillere; M Terme; N Merillon; J Taieb; F Sandoval; F Quintin-Colonna; K Lacerda; A Karadimou; C Badoual; A Tedgui; W H Fridman; S Oudard Journal: Cancer Metastasis Rev Date: 2011-03 Impact factor: 9.264