Table 1.
Changes in tumor immune microenvironment of preneoplastic lesions and lung cancer.
| Pan lung cancer preneoplasia | Lung cancer preneoplasia | Lung cancer |
|---|---|---|
| ↓ Th1-dervied IFN-γ ↑ Th2 in Barret esophageal tissue ↑ Pro-inflammatory mediators (IL-17A, IFN-γ, IL-6) in OPLs (188, 189) |
↓ Anti-tumor Th1 (IL12A, GZMB) ↑ Pro-tumorigenic Th2 ↑ Pro-inflammatory cytokines (IL-6, TNF-α) in AAH (190, 191) |
↓ Anti-tumor Th1 (IL12A) ↑ Pro-tumorigenic Th2 ↑ Immune suppressive mechanisms (IL6, IL10) (191, 192) |
| ↑ Immune checkpoints (PD-L2, LAG-3) in Lynch syndrome (193) |
↑ Immune checkpoints (CTLA-4, CCR2) (191) |
↑ Immune checkpoints (PD-1, CTLA−4, VISTA, LAG−3, TIM-3) (191) |
| ↑ CD4+ and CD8+ TILs (194) |
↑ Exhausted CD8+ TILs reactive to neoantigens (195) | ↓ Cell–mediated immune response (195) |
| Uncontrolled TLR signaling (196, 197) |
↑ TLR and inflammatory mediators (NF–κB) ↑ downstream chemokines (IL-6, IL−17) (198) |
↓ TLR, ↓ Effector cytokine production (IFN–γ, TNF–α) (199) |
| Progressive infiltration of innate immunosuppressive cells and M2 macrophages and T regs in OPLs (188, 200) |
Immature macrophage-lineage cell infiltration (201) |
Massive tumor immune cell infiltration (201) |
| ↑ B-cell chemotaxis (↑ CXCL13, CXCL14) (202) |
↑ B-cell chemotaxis (↑ CXCL13, CXCL14) (191) |
↑ B-cell chemotaxis (↑ CXCL13, CXCL14) (191) |
| Common tumor antigens between cancers and PMLs (203) |
↑ Neoantigen expression in due to infiltration of CD4+ and CD8+ T cell as well as ↑ PD-1 (179) |
↑ Immunogenic neoantigen load activating anti-tumor T cell response (195) |
| Humoral cell-mediated immune response activated against TAA in gastric premalignant lesions (204) |
Activation of cell-mediated immune response and recognition of neoepitopes (179) |
Activation of cell-mediated immune response and recognition of neoepitopes (179) |
| Very few chromosomal mutations (TP53 in Barret's esophagus) (205) |
↓ Somatic mutational processes (TP53) (205) |
↑ Tumor mutational landscape (KRAS, BRAF, EGFR, TP53) (205) |
| AI in oropharyngeal epithelial dysplastic lesions (LOH and MSI) (206) |
Genome-wide spatial gradient of AI next to tumor sites (205) |
Genome-wide spatial gradient of AI next to tumor sites (205) |
| LOH in chromosomal arms 3p, 17p, 13q in OPLs (207) |
LOH in chromosomal arms: 17p, 13q, 19pl, and 9q (191) |
LOH in chromosomal arms: 17p, 13q, 19p, and 9q (191) |
| Epigenetic changes in oral PML (TP53, CDKN2A, PIK3CA, HRAS)
(208) |
Epigenetic modifications (CDKN2A) and differential gene expression patterns in AAHs (205) |
Epigenetic modifications (CDKN2A) and differential gene expression patterns in AAHs (209) |
OPL, oral premalignant lesions; TILs, tumor infiltrating lymphocytes; TLR, Toll-like receptor; T reg, regulatory T cell; PML, premalignant lesion; TAA, tumor-associated antigen; LOH, loss of heterozygosity; MSI, microsatellite instability; AI, allelic imbalance; AAH, atypical adenomatous hyperplasia.