Effects of helicobacter pylori on tumor microenvironment and immunotherapy responses

Abstract

Helicobacter pylori is closely associated with gastric cancer. During persistent infection, Helicobacter pylori can form a microenvironment in gastric mucosa which facilitates the survival and colony formation of Helicobacter pylori. Tumor stromal cells are involved in this process, including tumor-associated macrophages, mesenchymal stem cells, cancer-associated fibroblasts, and myeloid-derived suppressor cells, and so on. The immune checkpoints are also regulated by Helicobacter pylori infection. Helicobacter pylori virulence factors can also act as immunogens or adjuvants to elicit or enhance immune responses, indicating their potential applications in vaccine development and tumor immunotherapy. This review highlights the effects of Helicobacter pylori on the immune microenvironment and its potential roles in tumor immunotherapy responses.

Keywords: Helicobacter pylori; gastric cancer; immune evasion; immunotherapy; microenvironment.

Figure 1

Effects of H. pylori on tumor stromal cells and tumor-related proteins in gastric tumor immune microenvironment. Arg, arginase; ASK1, apoptosis signal-regulating kinase 1; BM-MSC, Bone marrow-derived mesenchymal stem cells; CAF, cancer-associated fibroblast; Cag A, cytotoxin-associated gene A; CXCL8, chemokine (C-X-C motif) ligand 8; EMT, epithelial-mesenchymal transition; hA-MSC, human adipose-derived mesenchymal stem cells; HH, Hedgehog; HO-1, heme oxygenase-1; H.pylori, Helicobacter pylori; IL-22, Interleukin-22; IRF, interferon regulatory factor; IFN, interferon; KLF4, Krüppel-like factor 4; LPS, lipopolysaccharide; MAPK, mitogen-activated protein kinases; MDSCs, myeloid-derived suppressor cells; MET, mesenchymal-epithelial transition; MHC-II, major histocompatibility complex class II; MMP, matrix metalloproteinase; mTOR, mammalian target of rapamycin; Myh9, myosin heavy chain 9; NF-κB, nuclear factor kappa B; miR, microRNA; MSCs, mesenchymal stem cells; PD-1, programmed death 1; PD-L1, programmed death-ligand 1; PI3K-AKT, phosphatidylinositol 3 kinase-protein kinase B; ROS, reactive oxygen species; SDF, stromal-derived factor; Shh, Sonic hedgehog; SLFN4, Schlafen 4; STAT3, signal transducer and activator of transcription 3; TAMs, tumor-associated macrophages; TGFβ, transforming growth factor β; TLR, Toll-like receptor; Ure, urease; Vac A, vacuolating cytotoxin A.

Figure 2

Effects and applications of H. pylori and its factors in tumor immunotherapies. Bab A, blood-group antigen-binding adhesin gene A; Cag A, cytotoxin-associated gene A; Chi-rNap, rNAP coated chitosan nanoparticles; DCs, dendritic cells; DLBCL, diffuse large B-cell lymphoma; HP-NAP, H. pylori neutrophil-activating protein; MDSCs, myeloid-derived suppressor cells; MV-NAP-uPAR, recombinant measles virus-NAP-urokinase-type plasminogen activator receptor; NSCLC, non-small cell lung cancer; OVs, oncolytic viruses; PD-L1, programmed death-ligand 1; rHP-NAP, recombinant H. pylori neutrophil-activating protein; rMBP-NAP, recombinant HP-NAP with the maltose-binding protein of Escherichia coli; Th cells, T helper cells; TIL-T cells, tumor-infiltrating T lymphocytes; TME, tumor microenvironment; Vac A, vacuolating cytotoxin A; VV-GD2m-NAP, vaccinia virus - neuroblastoma-associated antigen disialoganglioside mimotope.