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Infiltrating and peripheral immune cell analysis in advanced gastric cancer according to the Lauren classification and its prognostic significance.

Authors
  • Pernot, Simon1, 2
  • Terme, Magali3
  • Radosevic-Robin, Nina4
  • Castan, Florence5
  • Badoual, Cécile3, 6
  • Marcheteau, Elie3
  • Penault-Llorca, Fréderique4
  • Bouche, Olivier7
  • Bennouna, Jaafar8
  • Francois, Eric9
  • Ghiringhelli, Francois10
  • De La Fouchardiere, Christelle11
  • Samalin, Emmanuelle12
  • Baptiste Bachet, Jean13
  • Borg, Christophe14
  • Boige, Valérie15
  • Voron, Thibault3
  • Stanbury, Trevor16
  • Tartour, Eric3
  • Gourgou, Sophie5
  • And 2 more
  • 1 Université de Paris, PARCC, INSERM, 75015, Paris, France. [email protected] , (France)
  • 2 Hôpital Européen Georges-Pompidou, APHP; Department of GI oncology, Université de Paris, Paris, France. [email protected] , (France)
  • 3 Université de Paris, PARCC, INSERM, 75015, Paris, France. , (France)
  • 4 Department of Biopathology, Centre Jean Perrin and University Clermont Auvergne/INSERM U1240, Clermont-Ferrand, France. , (France)
  • 5 Biometrics Unit, Institut du Cancer Montpellier-Val d'Aurelle, Université de Montpellier, Montpellier, France. , (France)
  • 6 Department of Pathology, Université de Paris, Sorbonne Paris Cité, Paris, France. , (France)
  • 7 CHU Robert Debré, Reims, France. , (France)
  • 8 Institut de Cancérologie de l'Ouest-Site René Gauducheau, Saint Herblain, France. , (France)
  • 9 Centre Antoine-Lacassagne, Nice, France. , (France)
  • 10 Centre Georges-François Leclerc, Dijon, France. , (France)
  • 11 Centre Léon Bérard, Lyon, France. , (France)
  • 12 Institut du Cancer Montpellier-Val d'Aurelle, Université de Montpellier, Montpellier, France. , (France)
  • 13 Pitié Salpétrière Hospital, Paris, France. , (France)
  • 14 Medical Oncology Unit, CHU Minjoz, Besancon, France. , (France)
  • 15 Département de Médecine Oncologique, Gustave Roussy, Université Paris-Saclay, 94805, Villejuif, France. , (France)
  • 16 UNICANCER, Paris, France. , (France)
  • 17 Hôpital Européen Georges-Pompidou, APHP; Department of GI oncology, Université de Paris, Paris, France. , (France)
Type
Published Article
Journal
Gastric cancer : official journal of the International Gastric Cancer Association and the Japanese Gastric Cancer Association
Publication Date
Jan 01, 2020
Volume
23
Issue
1
Pages
73–81
Identifiers
DOI: 10.1007/s10120-019-00983-3
PMID: 31267360
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

The correlation between immune cells and the Lauren classification subtypes and their prognostic impact in advanced gastric cancer (AGC) are unknown. 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. 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). 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.

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