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Summary Recent advances in chronic lymphocytic leukaemia (CLL) treatment, more particularly through upfront use of anti‐CD20 monoclonal antibodies, have prolonged patient progression‐free survival. Nonetheless, apart from allogeneic stem cell transplantation, no curative treatment is available. One possible explanation for the lack of cure in CLL could be a defective immune anti‐tumour response. As the result of abnormal HLA class I molecule expression, CLL cells escape from specific T‐lymphocyte immunity but should be the target for the innate natural killer (NK) cell‐mediated immune response. Defective NK cytotoxicity as the result of decreased expression of the natural cytotoxicity receptors (NCRs) NKp30/NCR3, NKp44/NCR2 and NKp46/NCR1 has been described in haematological malignancies such as acute myeloid leukaemia. This prompted us to focus our attention on NCR expression on NK cells from patients with CLL. Although we failed to detect any difference between CLL patients and healthy age‐matched controls, a precise analysis of clinical data showed a correlation between decreased NCR expression and poor prognosis factors such as low haemoglobin level, high (> 30 × 109 per litre) lymphocyte count or elevated C‐reactive protein. Together, these observations support the rationale for restoration of normal NK cell functions in patients with CLL, putatively through the use of immune therapy protocols that already have demonstrated some benefit in acute myeloid leukaemia such as interleukin‐2 plus histamine dihydrochloride.

SummaryIn monoclonal gammopathies (MG) and multiple myeloma (MM), normal natural cytotoxicity receptors (NCR) expression (NCR1/NKp46, NCR2/ NKp44, NCR3/NKp30) is observed in natural killer (NK) cells. Nonetheless, except in plasma cell leukemia, few tumor plasmocytes are present in PB, while NK studies have been performed on peripheral blood (PB). For this reason we focused our attention on NK from bone marrow (BM). Our study demonstrates that the down-regulation of NCR3/NKp30 is only detectable in NK from BM but not in PB, and shows a drastic decrease of both NKG2D and CD244/2B4/p38 expression in NK from BM in comparison with PB. In conclusion, our data more precisely describe the mechanism of immune escape of MG/MM from innate immunity since we show a drastic down regulation of 3 major activating NK receptors (NCR3/ NKp30, NKG2D and CD244/2B4/p38) at the site of tumor, i.e BM, that was undetectable in PB. Further studies regarding immune regulatory drugs in MG/MM will imperiously require the assessment of immune cell status not only in PB but also in BM to obtain more relevant data regarding anti-tumor efficacy.

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