TY - JOUR
T1 - Infiltrating and peripheral immune cell analysis in advanced gastric cancer according to the Lauren classification and its prognostic significance
AU - Pernot, Simon
AU - Terme, Magali
AU - Radosevic-Robin, Nina
AU - Castan, Florence
AU - Badoual, Cécile
AU - Marcheteau, Elie
AU - Penault-Llorca, Fréderique
AU - Bouche, Olivier
AU - Bennouna, Jaafar
AU - Francois, Eric
AU - Ghiringhelli, Francois
AU - De La Fouchardiere, Christelle
AU - Samalin, Emmanuelle
AU - Baptiste Bachet, Jean
AU - Borg, Christophe
AU - Boige, Valérie
AU - Voron, Thibault
AU - Stanbury, Trevor
AU - Tartour, Eric
AU - Gourgou, Sophie
AU - Malka, David
AU - Taieb, Julien
N1 - Publisher Copyright:
© 2019, The International Gastric Cancer Association and The Japanese Gastric Cancer Association.
PY - 2020/1/1
Y1 - 2020/1/1
N2 - 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.
AB - 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.
KW - Advanced gastric adenocarcinoma
KW - Biomarker
KW - CD8 T lymphocytes
KW - Natural killer cells
KW - Regulatory T cells
UR - http://www.scopus.com/inward/record.url?scp=85068761117&partnerID=8YFLogxK
U2 - 10.1007/s10120-019-00983-3
DO - 10.1007/s10120-019-00983-3
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C2 - 31267360
AN - SCOPUS:85068761117
SN - 1436-3291
VL - 23
SP - 73
EP - 81
JO - Gastric Cancer
JF - Gastric Cancer
IS - 1
ER -