The superiority of alternating chemotherapy and radiotherapy over radiotherapy alone in treating unresectable squamous cell carcinoma of the head and neck seen at 3 years was confirmed at 5 years. However, additional trials must be conducted before considering the combined approach as standard therapy.
Several chemokines/chemokine receptors such as CCR7, CXCR4 and CXCR5 attract chronic lymphocytic leukemia (CLL) cells to specific microenvironments. Here we have investigated whether the CX 3 CR1/CX 3 CL1 axis is involved in the interaction of CLL with their microenvironment. CLL cells from 52 patients expressed surface CX 3 CR1 and CX 3 CL1 and released constitutively soluble CX 3 CL1. One third of these were attracted in vitro by soluble CX 3 CL1. CX 3 CL1-induced phosphorylation of PI3K, Erk1/2, p38, Akt and Src was involved in induction of CLL chemotaxis. Leukemic B cells upregulated CXCR4 upon incubation with CX 3 CL1 and this was paralleled by increased chemotaxis to CXCL12. Akt phosphorylation was involved in CX 3 CL1-induced upregulation of CXCR4 on CLL. In proliferation centers from CLL lymph node and bone marrow, CX 3 CL1 was expressed by CLL cells whereas CX 3 CR1 was detected in CLL and stromal cells. Nurselike cells (NLCs) generated from CLL patient blood co-expressed surface CX 3 CR1 and CX 3 CL1, but did not secrete soluble CX 3 CL1. Only half of NLC cell fractions were attracted in vitro by CX 3 CL1. In conclusion, the CX 3 CR1/CX 3 CL1 system may contribute to interactions between CLL cells and tumor microenvironment by increasing CXCL12-mediated attraction of leukemic cells to NLC and promoting directly adhesion of CLL cells to NLC.
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