Complex role for the immune system in initiation and progression of pancreatic cancer

Table 1 Major functions of the innate immune cells in both inflammation and cancer

Inflammatory cell	Immune function	Role in cancer
Neutrophil	Secretion of cytokines/chemokines to modulate other cells in the immune response	Maintenance of pro-angiogenic phenotype[242]
	Release of cytotoxic granules	Suppression of anti-tumor immunity[243]
	Phagocytosis	Promotion of metastasis[244]
Mast cell	Release of cytotoxic granules	Suppression of anti-tumor immunity[245]
	Enhancement of immune cell recruitment	Stimulation of angiogenesis[152]
	Permeabilization of blood vessels	Direct stimulation of cancer cell growth[246]
		Secretion of mitogenic factors[157]
Macrophage	Phagocytosis
	Promotion of T-lymphocyte activation
M1	Initiation of immune cell response
	Antigen presentation
M2	Wound repair
	Immunosuppression
	Tissue remodeling
	Resolution of immune response
TAM		Secretion of Arginase-1[19]
		Support of Treg activation[247,248]
		Promotion of angiogenesis[16]
		Enhancement of tumor metastasis[17]
MDSC	Suppression of NKC and T-lymphocyte activation	Production of ROS[22]
		Secretion of peroxynitrite[23]
		Secretion of Arginase-1[24,25]
		Induction of Treg[26]
		Depletion of cysteine[27]
NKC	Release of cytotoxic granules	Tumor cytotoxicity[28]
DC	Antigen presentation

TAM: Tumor-associated macrophage; MDSC: Myeloid-derived suppressor cell; NKC: Natural killer cell; DC: Dendritic cells.

Table 2 Cytokines released during pancreatic injury

Cytokine	Expressed by	Acts on
GM-CSF	Acini[194]	Neutrophils[231], MDSCs[194]
IL-1β	Acini[104,238], activated macrophages[237], neutrophils[236]	Macrohpage (inhibition)[227]
IL-6	Acini[239], monocytes[30], macrophages[30], endothelial cells[30] fibroblasts[30], smooth muscle cells[30], IL-1b[30], TNFα[30]	CRP[228,229], T-lymphocyte[30], DCs (inhibition)[174]
IL-8	Acini[105], IL-1[241], TNFα[241], macrophages[241], neutrophils[235]	Neutrophils[223]
IL-10	Acini[240], Treg[233]	T-lymphocytes (inhibition)[233], DCs (inhibition)[174], macrophages (inhibition)[232,234]
IL-12	Activated macrophages[231], dendritic cells[30]	NKCs[231]
IL-33	Acini[105]	Mast cells[103]
KC	Acini[105], monocytes and neutrophils[250	Neutrophils[225]
MCP-1	Acini[105]	Macrophages[230]
MIP-2	Acini[105], activated macrophages and neutrophils[93	Neutrophils[224]
TNFα	Acini[105], activated macrophages[99], neutrophils[236], mast cells[226]	Neutrophils[226], NKC[231]

IL: Interleukin; MCP-1: Monocyte chemotactic protein-1; MIP-2: Macrophage inflammatory protein 2; TNFα: Tumor necrosis factor-α; MDSC: Myeloid-derived suppressor cell; NKC: Natural killer cell; DC: Dendritic cells.