Clinical impact of chemotherapy to improve tumor microenvironment of pancreatic cancer

Table 1 Targets of chemotherapy to improve tumor microenvironment

Cellular components	Target molecules	Chemotherapeutic agents	Underlying mechanism	Ref.
TIL	CD4, CD8 positive T lymphocytes RAS/MAPK	GEM, TS-1, MEK inhibitor, PD1/PDL1 immune checkpoint inhibitors	Increase lymphocyte infiltration	[22] [24]
DC		GEM	Proliferation of DC and CTL	[26]
Treg	CD4 and FoxP3 positive T lymphocytes	GEM, cyclophosphamide	Depletion	[21]
MDSC	CCL2, CCR2, GMCSF	GEM, 5-FU	Increase differentiation Depletion	[34,35]
				[5]
CAF	Palladin positive fibroblasts	GEM	Depletion	[38]
	mTOR/4E-BP1 pathway	GEM, Pasireotide	Reduce tumor growth and chemoresistance	[39]

TIL: Tumor infiltrating lymphocytes; DC: Dendritic cells; Treg: Regulatory T cells; TAM: Tumor associating macrophages; MDSC: Myeloid derived suppressor cells; CAF: Cancer associated fibroblasts; Gem: Gemcitabine; 5-FU: 5-fluorouracil.