Table 2.
Malignancies implicated to utilize gamma(c) cytokines
| Cytokine | Malignancy | Evidence | Ref. |
|---|---|---|---|
| IL-2 | Hodgkin disease | IL-2R+ or CD25+ by IHC | [34, 35] |
| B- and T-cell lymphomas | IL-2+ or IL-2R+ or CD25+ by IHC IL-2mRNA in CD25+ cells IL-2 can signal and promotes proliferation |
[34–37, 42] | |
| T-cell leukemias | Aberrant expression CD25mRNA | [38] | |
| B-cell CLL | CD25+ and CD122+ by antibody and mRNA analysis IL-2 induces proliferation of CD25+ cells |
[39] | |
| Head and neck carcinoma | Surface IL-2+ and CD122+ and intracellular IL-2+ by flow cytometry Anti-CD25 treatment induces G1 arrest and induces apoptosis in vitro |
[40, 41] | |
| Gastric carcinoma | Surface IL-2+ and CD122+ and intracellular IL-2+ by flow cytometry | [40] | |
| Squamous cell lung carcinoma | IL-2+ and CD25+ by IHC | [37] | |
| IL-7 | Acute B-cell leukemia | IL-7R mRNA+, IL-7R protein+ and shows in vitro kinase activity Growth inhibition by rapamycin reversed by IL-7 CD127 is alternatively spliced |
[58, 60, 61, 64] |
| Acute T-cell leukemia | Notch1 binds to IL-7R promoter, regulates IL-7R transcription and CD127 expression | ||
| Hodgkin disease | IL-7R+ by flow cytometry and IHC IL-7 stimulates growth in colony assays IL-7 prevents apoptosis in serum-free assays |
[62] | |
| Lung carcinoma | IL-7R mRNA+, IL-7R protein+ and in vitro kinase activity IL-7 induces VEGF-D and promotes lymphangiogenesis |
[58, 59] | |
| Brain tumors | IL-7R is alternatively spliced | [64] | |
| IL-15 | Large granular leukemia | IL-15 stimulates proliferation IL-15 induces all known signaling deregulations |
[105, 106] |
| CLL | IL-15 causes receptor signaling, proliferation and prevents apoptosis Cells stimulated with CD40 exhibit increased expression of IL-15R |
[107] | |
| Pediatric ALL | High IL-15 expression correlates with CNS involvement | [111] | |
| Cutaneous T cell lymphoma | IL-15 can signal and promote proliferation | [42] | |
| Renal cell carcinoma | IL-15R+ by flow cytometry and RT-PCR IL-15 can signal IL-15R |
[109] | |
| Head and neck carcinoma | IL-15Ra+ by RIA | [108] | |
| IL-21 | T cell leukemia | IL-21R+ by flow cytometry and RT-PCR IL-21 induces signaling and proliferation |
[140] |
| Hodgkin disease | IL-21+ by flow cytometry, RT-PCR and IHC IL-21R+ by flow cytometry IL-21 signals STAT5 to cause proliferation IL-21 protects cells from apoptosis |
[156, 157] | |
| B- and T-cell lymphomas | IL-21R+ by flow cytometry IL-21 causes proliferation |
[140] | |
| Multiple myeloma | IL-21 signals and is a growth factor via an IGF-1 autocrine loop | [158] |
IHC = Immunohistochemistry, CNS = central nervous system, RT-PCR = reverse transcriptase polymerase chain reaction, RIA = radioimmunoassay