Table 1.

Overview of preclinical studies in vivo reporting immunomodulatory effects of STF in the context of cancer treatment.

Author	Mouse Model	Treatment	Outcome, Findings
Pietrocola et al., 2016 [3]	Autophagy competent TC-1 non-small cell lung cancer	Hydroxycitrate + MTX or OX	Improved tumor growth control mediated by Treg depletion; autophagy required
	Colorectal cancer	Hydroxycitrate + MTX or OX	Improved tumor growth control mediated by Treg depletion; autophagy required
	MCA205 fibrosarcoma	Hydroxycitrate + MTX or OX Hydroxycitrate + cisplatin 48-h STF	Improved tumor growth control mediated by Treg depletion; autophagy required Tumor growth control not improved; autophagy induction similar to hydroxycitrate
Di Biase et al., 2016 [4]	4T1 breast cancer, B16 melanoma	2–3 cycles, 4-day FMD every 2 weeks + DXR or CP	Delayed tumor progression; intratumoral Treg reduction, HO-1 dependent; increased CD8+ TILs
			Increased CLP in bone marrow, increased circulating naïve T cells
Takakuwa et al., 2019 [37]	C57Bl/6 mice	48-h STF	Increased naïve CD4 and CD8 T cells in bone marrow
Collins et al., 2019 [38]	C57Bl/6 mice (several types), with B16 melanoma cell line	Calorie reduction 50% for 6 weeks	Central accumulation memory T cells associated with ↑tumor immunity and survival benefit; transient peripheral ↓CD4 & CD8 T cells (1 w); central increase CD4 and CD8 T cells (at 3 w)
Cheng et al., 2015 [39]	C57BL/6 J mice	48–120 h STF around CP administration for 6 cycles in 12–14 days	Hematopoietic stem cell regeneration, IGF-1/PKA dependent; reduced chemotherapy induced mortality; reduced DNA damage in bone marrow cells
Pomatto-Watson et al., 2021 [40]	4T1 breast cancer	4-day FMD, 2 cycles in 28 days	Reduced MDSCs frequency in spleen; intratumoral MDSC frequency; increased T cell to MDSC ratio in PBMC
Sun et al., 2017 [36]	Colorectal cancer, in vivo	Alternate day fasting for 2 weeks	Tumor growth inhibition; less M2 polarization of macrophages
	CT26 and RAW264.7 cells, in vitro		Mechanism in vitro: CD73 reduction, blunted adenosine release into ECM

MTX mitoxantrone, OX oxaliplatin, DXR doxorubicin, CP cyclophosphamide, STF short-term fasting, FMD fasting mimicking diet, HO-1 heme oxygenase-1, Treg regulatory T cell, TIL tumor infiltrating lymphocytes, CLP common lymphoid progenitor, IGF-1 insulin growth factor 1, PKA protein kinase A, MDSC myeloid derived suppressor cells, PBMC peripheral blood mononuclear cells, ECM extracellular matrix.