. 2021 Jul 30;13(15):3856. doi: 10.3390/cancers13153856

Table 2.

Alterations of cytokine levels and their correlation with biological characteristics and/or prognosis in patients with CLL.

Cytokines	Alteration Compared to Healthy Controls	Correlation with Biological Characteristics and/or Prognosis	Ref.
sCD8	Increased	Active disease, advanced Rai stage.	[120]
sCD27	Increased	Advanced Rai stage, elevated β₂-microglobulin.	[121]
sIL-2R	Increased	Active disease, advanced Rai stage, high lymphocyte count.	[120]
IL-6	Increased	Advanced Rai stage, previous treatment, elevated β₂-microglobulin, elevated LDH, worse OS *.	[104]
	Increased	Advanced Binet stage, previous treatment, non-CR status, presence of del(17p)/del(11q), shorter absolute LDT, worse TTFT, worse PFS.	[122]
	Increased	Elevated β₂-microglobulin. IL-6, IL-8 and TNFα levels correlated with each other. In patients ≥ 70 years, IL-6 is a better prognostic marker than IGHV mutational status.	[123]
IL-8	Increased	Active disease (progression from Binet stage A to B/C).	[124]
	Increased	Elevated β₂-microglobulin. IL-8, IL-6 and TNFα levels correlated with each other.	[123]
	Increased	Advanced Rai stage, elevated β₂-microglobulin.	[121,125,126]
IL-9	Increased	Advanced stage, elevated β₂-microglobulin, higher ZAP70 expression.	[127]
IL-9	Increased	Advanced Rai stage, higher ZAP70 and CD38 expression.	[128]
IL-10	Increased	Advanced Rai stage, previous treatment, elevated β₂-microglobulin, elevated LDH, worse OS *.	[104]
	Decreased	Active disease.	[129]
	Increased	High-risk and active disease. Worse TFS (in high-risk group, regardless of IGHV mutational status), worse OS ^§.	[130]
	Increased	Advanced Rai stage, elevated β₂-microglobulin.	[121]
IL-23R	Decreased	Worse prognosis in early stage CLL, worse TTFT.	[131]
TNFα	Increased	Advanced stage, elevated β_2-microglobulin, higher CD38 expression, presence of del(11q), tris(12), chromosome 17 aberrations, worse OS.	[132]
	Increased	High-risk and active disease. Worse TFS (in high-risk group, regardless of IGHV mutational status), worse OS ^§.	[130]
	Increased	Elevated β₂-microglobulin. IL-6, IL-8 and TNFα levels correlated with each other. In patients ≥ 70 years, IL-6 is a better prognostic marker than IGHV mutational status.	[123]
SDF-1 and uPAR	Increased	Advanced stage.	[113]
SDF-1 and CXCR4	Increased	Advanced Rai stage.	[133]
IGFBP-2, BMP-4, MCP-4	Decreased	Advanced stage.	[113]
CCR7	Increased	Advanced Rai stage.	[133]
CXCR3	Decreased	Advanced stage, higher CD38 expression, unmutated IGHV status, worse OS.	[134]
CX3CL1	Increased	Lymph node involvement, worse TTT, high risk of progression (especially in earlier stages of disease).	[135]
CX3CL1	Increased	Higher ZAP70 expression.	[136]
CCL3/MIP-1α	Increased	Advanced stage, higher CD38 and ZAP70 expression, unmutated IGHV status.	[137]

* IL-6 and IL-10 emerged as independent prognostic factors for OS both when analyzed individually and in combination. ^§ The cytokine low-risk group comprised patients with either low TNFα or low IL-10 or those with only one elevated parameter. The cytokine high-risk group comprised patients with both high TNFα and high IL-10.