Table 2.

Tregs-targeted immunotherapeutic strategies for colorectal cancer

Strategy Category	Target/ Molecule	Example Agent	Mechanism	Development Stage	Key Challenge	Refs
Depletion	CD25	Daclizumab, Basiliximab	Deplete CD25ʰⁱ Tregs	Preclinical / Early clinical (discontinued in oncology)	Also depletes activated Teff	103, 104, 156
	CCR4	Mogamulizumab	Deplete skin/gut-homing Tregs	Approved in CTCL; under investigation in CRC	Limited to CCR4⁺ subset	157-159
	GITR	DTA-1 (agonist)	Deplete Tregs + activate Teff	Preclinical	Agonism vs antagonism unclear	160
	TIGIT	Tiragolumab (Fc-competent)	FcγR-mediated Tregs depletion	Phase II/III	Requires Fc optimization	161
Functional modulation	FOXP3 stability	TMED4 inhibitor	Destabilize FOXP3, convert Tregs	Preclinical	Off-target effects	45
	Adenosine pathway	Anti-CD73, A2AR antagonist	Block Tregs-mediated metabolic suppression	Phase I/II	Tumor specificity	162
	PI3Kδ	Idelalisib	Inhibit Tregs proliferation	Preclinical	Sparing Teff	163
	HDAC	Entinostat	Epigenetic modulation of Tregs function	Phase II	Dual effects	164
Combination	PD-1 + Treg depletion	Anti-PD-1 + low-dose anti-CD25	Synergistic anti-tumor immunity	Preclinical	Toxicity profile	163 164