Reshaping the systemic tumor immune environment (STIE) and tumor immune microenvironment (TIME) to enhance immunotherapy efficacy in solid tumors

Table 4 Reshaping STIE and TIME with chemotherapy, target therapy, or combined therapy

Cancer type	STIE		TIME		REF
Cancer type	Cell	Immune regulator	Cell	Immune regulator	REF
NSCLC	↑: CD8⁺ T, Th1 cell -: PD-1⁺CD8⁺ T, PD-1⁺CD4⁺ T ↓: CD3⁺CD8⁺ T, Treg, Th2 cell, Th17 cell, NK	↑: IFN-γ ↓: ctDNA, IL-4, IL-17	↑: T cell, CD8⁺ T, Senescent CD28⁻CD57⁺ T, Highly differentiated CD8⁺CD28⁻ T, DC -: CD8⁺ TIL density in tumors with a high PD-L1 expression level ↓: CD8⁺ and FOXP3⁺ TIL densities	↑: PD-1, PD-L1, IL-2, CD73, CXCL10 ↓: FOXP3, CTLA4, LAG3, TNFRSF18, CD80	[198, 215, 226,227,228] [216, 217, 229,230,231]
HCC	↑: CD14⁺ Monocyte, CD56⁺ NK ↓: CD4⁺CD25⁺Foxp⁺ regulatory T	↑: ST6GAL1, Fas/FasL, MIR30A/15B/107/122/125B/200A/320/374B/645	↑: T cell proliferation and tumor infiltration, CD8⁺ T, CSC ↓: Numbers of tumor vessels and pericytes	↑: IL-1β, CXCL5, HIF-1α/2α ↓: NF‐kB, FGFR4, LIF/JAK1/STAT3, PD-L1/METTL3 on cancer	[211, 228, 232,233,234,235,236,237,238,239] [240, 241]
NPC	↓: CD3⁺ T, CD4⁺ T, CD8⁺ T	↑: CK-19, S-LDH	↑: T cell proliferation, tumor infiltration, CD8⁺ T, NK, PD-1⁺ NK	↑: PD-1, PD-L1, NF-κB, IL-2, CEBPA, miR-3188/PD-L1 on cancer	[228, 242,243,244,245,246,247,248]

T T cells, CSC cancer stem cell, NK natural killer, DC dendritic cell, AFP alpha-fetoprotein, ALC absolute lymphocyte count, TIL tumor-infiltrating immune cell (e.g., lymphocyte, APC antigen-presenting cells); CK-19 cytokeratin-19, S-LDH serum lactic dehydrogenase, ctDNA circulating tumor DNA; ↑, Upregulation; ↓, Downregulation; -, symbol: No significant change in the cited literature studies; ↑, ↓ and - reflected the changes in tumor tissue or cancer patients compared with adjacent normal tissue or non-cancer donors; REF reference

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