Regulatory molecules of CLL cells
| Characteristic . | Proposed mechanisms . | Reference . |
|---|---|---|
| IL-10 | Regulates inflammation, autoimmunity, adaptive and innate immune responses, regulates production of tumor necrosis factor-α by macrophages | 24 |
| CD5 | Promotes STAT3/NFAT2-mediated IL-10 secretion | 62 |
| CD23 | Associates with regulatory B-cell phenotype | 24 |
| CD24 | Associates with regulatory B-cell phenotype | 24 |
| CD25 | Reduces T-cell proliferative capacity, inhibits Th1 differentiation, and skews peripheral T cells toward Th2 response in tissue by IL2 deprivation | 63 |
| CD27 | Enhances survival of Tregs; induces hypogammaglobulinemia by interacting with CD70 on plasma cells | 64,65 |
| CD39/CD73 | Ectoenzymes producing immune suppressive adenosine to inhibit T-cell proliferation | 66,67 |
| CD80/CD86 | Induced on activated CLL cells; induce T-cell tolerance | 14,68 |
| CD152 (CTLA-4) | Acts as an “off” switch signal via B7.1/B7.2 (CD80/CD86) to control T-cell responses | 69 |
| CD178 (FasL) | Induces hypogammaglobulinemia by CD95(Fas)-mediated suppression of primary plasma cell function | 70 |
| CD200 | Induces impaired actin synapse formation of T cells; inhibits IL2 and IFN-γ production by CD4+ T cells; promotes Treg differentiation of CD4+ T cells; inhibits antigen-presenting cells | 14,71 |
| CD269 (BCMA) | Favors plasma cell death and hypogammaglobulinemia by BAFF/APRIL deprivation | 72,73 |
| CD270 | Induces impaired actin synapse formation of T cells | 14 |
| CD274 (PD-L1) | Induces mpaired actin synapse formation of T cells; enhances susceptibility to apoptosis on CD4+ T cells at late stages of disease; induces hypogammaglobulinemia by plasma cell apoptosis | 14,74,75 |
| CD276 (B7-H3) | Induces impaired actin synapse formation of T cells | 14 |
| CD279 (PD-1) | Inhibits IFN-γ production by CD8+ T cells | 76 |
| NAMPT | Expressed on activated CLL cells, polarizes monocytes differentiation toward M2 macrophages | 23 |
| HLA-G | Associates with lower serum IgG, higher serum IL-10, and lower CD4+ T cells | 77 |
| Characteristic . | Proposed mechanisms . | Reference . |
|---|---|---|
| IL-10 | Regulates inflammation, autoimmunity, adaptive and innate immune responses, regulates production of tumor necrosis factor-α by macrophages | 24 |
| CD5 | Promotes STAT3/NFAT2-mediated IL-10 secretion | 62 |
| CD23 | Associates with regulatory B-cell phenotype | 24 |
| CD24 | Associates with regulatory B-cell phenotype | 24 |
| CD25 | Reduces T-cell proliferative capacity, inhibits Th1 differentiation, and skews peripheral T cells toward Th2 response in tissue by IL2 deprivation | 63 |
| CD27 | Enhances survival of Tregs; induces hypogammaglobulinemia by interacting with CD70 on plasma cells | 64,65 |
| CD39/CD73 | Ectoenzymes producing immune suppressive adenosine to inhibit T-cell proliferation | 66,67 |
| CD80/CD86 | Induced on activated CLL cells; induce T-cell tolerance | 14,68 |
| CD152 (CTLA-4) | Acts as an “off” switch signal via B7.1/B7.2 (CD80/CD86) to control T-cell responses | 69 |
| CD178 (FasL) | Induces hypogammaglobulinemia by CD95(Fas)-mediated suppression of primary plasma cell function | 70 |
| CD200 | Induces impaired actin synapse formation of T cells; inhibits IL2 and IFN-γ production by CD4+ T cells; promotes Treg differentiation of CD4+ T cells; inhibits antigen-presenting cells | 14,71 |
| CD269 (BCMA) | Favors plasma cell death and hypogammaglobulinemia by BAFF/APRIL deprivation | 72,73 |
| CD270 | Induces impaired actin synapse formation of T cells | 14 |
| CD274 (PD-L1) | Induces mpaired actin synapse formation of T cells; enhances susceptibility to apoptosis on CD4+ T cells at late stages of disease; induces hypogammaglobulinemia by plasma cell apoptosis | 14,74,75 |
| CD276 (B7-H3) | Induces impaired actin synapse formation of T cells | 14 |
| CD279 (PD-1) | Inhibits IFN-γ production by CD8+ T cells | 76 |
| NAMPT | Expressed on activated CLL cells, polarizes monocytes differentiation toward M2 macrophages | 23 |
| HLA-G | Associates with lower serum IgG, higher serum IL-10, and lower CD4+ T cells | 77 |
APRIL, a proliferation-inducing ligand; BCMA, B-cell maturation antigen; BAFF, B-cell activating factor; CTLA-4 cytotoxic T-lymphocyte–associated protein 4; IFN-γ, interferon-gamma NAMPT, nicotinamide phosphoribosyltransferase; NFAT2, nuclear factor of activated T-cells 2; PD-1, programmed cell death protein 1; STAT3, signal transducer and activator of transcription 3.