Inflammation-related factors predicting prognosis of gastric cancer

Abstract

Gastric cancer (GC), which is mainly induced by Helicobacter pylori (H. pylori) infection, is one of the leading causes of cancer-related death in the developing world. Active inflammation initiated by H. pylori infection and maintained by inherent immune disorders promotes carcinogenesis and postoperative recurrence. However, the presence with H. pylori in tumors has been linked to a better prognosis, possibly due to the induction of antitumor immunity. Tumor infiltrations of tumor-associated macrophages, myeloid-derived suppressor cells, neutrophils, Foxp3(+) regulatory T cells are correlated with poor prognosis. Tumor infiltrating CD8(+) cytotoxic T lymphocytes, dendritic cells, and CD45RO T cells are generally associated with good prognosis of GC, although some subsets of these immune cells have inverse prognosis prediction values. High ratios of Foxp3(+)/CD4(+) and Foxp3(+)/CD8(+) in tumors are associated with a poor prognosis; whereas high Th1/Th2 ratio in tumors predicts a good prognosis. High levels of interleukin (IL)-6, IL-10, IL-32, and chemokine C-C motif ligands (CCL)7 and CCL21 in circulation, high expression of CXC chemokine receptor 4, chemokine C-C motif receptor (CCR)3, CCR4, CCR5, CCR7, hypoxia-inducible factor-1α, signal transducer activator of transcription-3, cyclooxygenase-2, and orphan nuclear receptor 4A2 in tumors are associated with an unfavorable prognosis. Increased serum levels of matrix metalloproteinases (MMP)-3, MMP-7, and MMP-11 and increased levels of MMP-9, MMP-12, and MMP-21 in tumors are consistently associated with poor survival of GC. Further emphasis should be put on the integration of these biomarkers and validation in large cohorts for personalized prediction of GC postoperative prognosis.

Innate Lymphoid Cells in Cancer

“…A predominant Th2 phenotype is correlated with a poor prognosis in patients with gastric cancer (49). In these tumors, an immunosuppressive microenvironment is maintained by the interaction between Th2 cells, myeloid-derived suppressor cells, and M2 macrophages (50).…”

Modern concepts of factors for gastric cancer progression

“…Высокий уровень T-reg лимфоцитов обычно ассоцииру-ется с ухудшением прогноза при злокачественных новообразова-ниях [59,64]. CD8 + T-лимфоциты обладают цитотоксической активно-стью по отношению к опухоли.…”

“…CD8 + T-лимфоциты обладают цитотоксической активно-стью по отношению к опухоли. Большинство исследований сви-детельствует, что высокое содержание CD8 T-лимфоцитов и вы-сокое отношение CD8/CD4 в строме опухоли связано с лучшим прогнозом при злокачественных новообразованиях [64][65][66].…”

“…Хемокины инду-цируют продукцию макрофагами ангиогенных факторов, VEGF и ММР, разрушающих клеточный матрикс и способствующих миграции опухолевых и лимфоидных клеток [50,54,68,69]. Раз-личают М1 макрофаги, ассоциированные с острым воспалением и противоопухолевой активностью, и М2 макрофаги, связанные с опухолевой прогрессией [50,64,67,69,70].…”

Hyperactive gp130/STAT3‐driven gastric tumourigenesis promotes submucosal tertiary lymphoid structure development

“…Two major contributing factors to the poor overall survival rate (<25%) in GC are late diagnosis and the limited effectiveness of current treatment options. These factors are compounded by the heterogeneity of the host mucosal immune response and the diverse molecular complexity of gastric adenocarcinomas 2, 3. Thus, intra‐ and inter‐tumour heterogeneity present challenges to identifying robust biomarkers, that can aid early detection of disease and inform personalised treatment strategies for GC patients.…”