Immunosuppressive tumor microenvironment shape pancreatic cancer unresponsive to current immunotherapies

Table 1 Therapeutic strategies targeting immunosuppressive cells in pancreatic ductal adenocarcinoma

Target	Strategy	Core mechanism	Example agents
Tregs	Depletion	Anti-CD25 depletion	Basiliximab mogamulizumab
		Anti-CCR4 blockade
	Functional inhibition	TGF-β pathway blockade	Galunisertib oleclumab/ciforadenant
		Adenosine axis blockade
	Reprogramming	Selective IL-2Rβγ activation	Bempegaldesleukin THOR-707
MDSCs	Block recruitment	CCR2 inhibition	PF-04136309 plerixafor/BL-8040
		CXCR4 inhibition
	Induce differentiation	Retinoic acid-induced maturation	ATRA
	Selective depletion	Cytotoxic targeting of proliferating cells	Gemcitabine
TAMs	Depletion	CSF1R signaling inhibition	Pexidartinib
	Repolarization	CD40 activation	Sotigalimab motolimod eganelisib
		TLR activation
		PI3Kγ inhibition

TGF-β: Transforming growth factor β; IL: Interleukin; Treg: Regulatory T cells; TAM: Tumor-associated macrophages; MDSCs: Myeloid-derived suppressor cells; CCR4: C-C motif chemokine receptor 4; CCR2: C-C motif chemokine receptor 2; CSF1R: Colony-stimulating factor 1 receptor; TLR: Toll-like receptor; PI3Kγ: Phosphoinositide 3-kinase γ; ATRA: All-trans retinoic acid.