Table 1.

Factors affected by the obese state. Local and (potentially) systemic factors affected by the obese state, with the relevant hallmarks/enabling characteristics of cancer they may influence. Factors are grouped by type, and exemplar references are given. Downstream effectors related to these factors (e.g. TP53, ATR, AHR and HIF1α) are discussed in the main text. Key: SPS, sustaining proliferative signaling; EGS, evading growth suppressors; RCD, resisting cell death; ERI, enabling replicative immortality; IA, inducing angiogenesis; AIM, activating invasion and metastasis; TPI, tumour-promoting inflammation; AID, avoiding immune destruction; GIM, genome instability and mutation; REM, reprogramming energy metabolism

Factor	Direction in obesity	Associated hallmarks	Organism	Tissue	Exemplar reference(s)
Adipokines
Adiponectin	↓	EGS, IA, AIM	Human	Plasma	[12]
Leptin	↑	SPS, RCD, ERI, IA, AID, REM	Human	Serum	[13]
Resistin	↑	ERI, AIM	Human	Serum	[14]
Dietary factors
27-hydroxycholesterol	Postulated to be ↑	AID	Human	Serum	[15]
Chymotrypsin	Postulated to be ↑	EGS	Rat	Pancreas	[16]
Fatty acids (profiles need further elucidation)	↑	GIM, REM	Human	Serum	[17]
Glucose	↑	SPS, GIM, REM	Human	Plasma	[18]
Kynurenine	↑	SPS, RCD, IA, AID	Human	Plasma	[19]
PCSK9	↑	AIM	Human	Serum	[20]
Oncometabolites
Deoxycholic acid	↑	TPI	Mouse models	Serum	[21]
Lipid peroxides (e.g. measured by malondialdehyde)	↑	GIM	Human	Serum	[22]
ROS	↑	GIM, TPI, REM	Rat	Colon/Kidney	[23]
LPS	↑	TPI	Human	Serum	[24]
Cytokines and cytokine-like proteins
CCL5	↑	AIM	Mouse models	Lungs/Lymph nodes	[25]
CCL7	↑	AIM	Human	Periprostatic adipose tissue	[26]
IFNγ	↑	TPI	Human	Serum	[27]
IL-1β	↑	AIM, GIM, TPI, AID	Human	Adipose	[28]
IL-6	↑	SPS, RCD, AIM, GIM, TPI, AIM	Human	Plasma	[29]
IL-8	↑	AIM	Human	Serum	[30]
IL-10	↓	AID	Human	Serum	[31]
IL-12	↑	TPI	Human	Serum	[27]
IL-18	↑	GIM, TPI, AID	Human	Adipose/Plasma	[32]
MCP-1	↑	AID	Human	Serum	[33]
TNFα	↑	SPS, EGS, IA, AIM, TPI, AID	Human	Serum	[34]
TGFβ1	↑	EGS, RCD, IA, AIM, AID	Human	Plasma	[35]
Immune cells, markers and their products
iNKT cells	↓	AID	Human	Omentum	[36]
B cells (exhausted)	↑	AID	Ex vivo	Adipose	[37]
CD8 + T cells	↑	TPI, AID	Mouse models	Adipose	[38]
Eosinophils	↓	TPI, AID	Mouse models	Adipose	[39]
MAIT cells	↓	AID	Mouse models	Adipose/Ileum	[40]
MDSCs	↑	AID	Human	Serum	[41]
MMes	↑	TPI	Human	Adipose	[42]
NETs	↑	AIM	Human	Serum	[43]
Pro-inflammatory macrophages	↑	TPI	Mouse models	Adipose	[44]
Th1 cells	↑	TPI	Mouse models	Adipose	[45]
Th2 cells	↓	TPI	Mouse models	Adipose	[46]
Treg cells	↓	TPI, AID	Mouse models	Adipose	[47]
Proteins of the fibrinolytic system
PAI-1	↑	AIM	Human	Adipose	[48]
Tissue factor	↑	IA	Mouse models	Various (incl. Adipose/Liver)	[49]
Hormones
Cholecystokinin	↑	SPS	Mouse models	Pancreas	[50]
Insulin	↑	SPS, AIM, GIM, TPI, REM	Human	Plasma	[51]
Oestrogen	↑	SPS, GIM	Human	Plasma	[52]
Growth factors and their binding proteins
FGF19	↓	Potentially REM	Human	Serum	[53]
FGF21	↑	REM	Human	Serum	[54]
FGF23	↑	SPS	Human	Serum	[55]
HGF	↑	IA	Human	Serum	[56]
IGF-1	Controversial	SPS, RCD, AIM			[57–60]
IGF-2	↑	SPS	Human	Serum	[61]
IGFBP-2	↓	SPS, RCD, AIM	Human	Serum	[62]
IGFBP-3	Controversial	SPS			[63, 64]
PlGF	↑	IA, TPI	Human	Serum	[65]
VEGF-A	↑	RCD, IA	Human	Serum	[66]
VEGF-C	↑	IA	Human	Serum	[66]
VEGF-D	↑	IA	Human	Serum	[66]
Extracellular matrix components and remodelling
Collagen VI	↑	RCD, AIM, TPI	Mouse models	Adipose	[67]
Endotrophin	↑	RCD, TPI	Mouse models	Adipose	[67]
Certain MMPs   e.g. MMP-2	↑	AIM	Cell lines		[68]
Other salient species
AEBP1	↑	EGS	Mouse models	White adipose tissue	[69]
A-FABP	↑	SPS, REM	Human	Plasma	[70]
ANGPTL2	↑	IA, AIM	Human/Mouse models	Serum	[71]
Certain exosomal miRNAs   e.g. miR-122	↑	AIM, REM	Mouse models		[72]
Certain free miRNAs   e.g. miR-27a	↑	AIM	Cell lines		[73]
Ceruloplasmin	↑	IA	Human	Adipose/Plasma	[74]
SDF-1	↑	AIM	Mouse models	Adipose	[75]