Inhibition of leukemic cell proliferation by factor(s) released from irradiated lymphocytes of B‐chronic lymphocytic leukemia patients

Abstract

An attempt was made to clarify the mechanism by which splenic irradiation in patients with B-chronic lymphocytic leukemia (B-CLL) can induce a reduction in lymph node size. For this purpose peripheral blood lymphocytes from B-CLL patients were exposed to cobalt irradiation and were cultured for 1-8 days. The effect of the supernatants on the proliferation capacity of normal and malignant human cells was examined. A suppression of phytohemagglutinin (PHA)-induced proliferation of autologous and heterologous B-CLL lymphocytes was observed, whereas there was no effect on the proliferation of lymphocytes obtained from healthy volunteers. In addition, supernatants of irradiated B-CLL lymphocytes inhibited thymidine incorporation into blasts derived from patients with acute leukemia and the lymphoblastoid cell line Daudi, but they did not exert any effect on normal cells obtained from human embryonic liver. These results suggest the secretion of some factor(s) by irradiated B-CLL lymphocytes, which may inhibit the proliferation of malignant cells but has no effect on normal cells.

Low‐dose palliative splenic irradiation in haematolymphoid malignancy

“…It is still not entirely clear how splenic irradiation works. Different hypotheses have been proposed, including direct radiation induced lymphoid cell death, immune modulation by proportional change of lymphocyte subsets and induction of cytokines 25–29 …”

“…It is now primarily used as palliative treatment. Despite its long history, there is little evidence in published work to [25][26][27][28][29] Historically, SI has been planned using external photon beams with AP/PA parallel-opposed portals to encompass the whole spleen or part thereof. Weinmann et al 25 Computed tomography planning with exact data about dose distribution to the spleen and normal tissues is not routinely practised at our centre for palliative SI.…”

Peripheral blood complete remission after splenic irradiation in Mantle-Cell Lymphoma with 11q22-23 deletion and ATM inactivation

“…Secondly, an immune modulation via proportional changes of lymphocyte subsets has been advocated as a key event: in this case the differential cell killing of normal lymphocytes (due to known differences in intrinsic radiosensitivity) is believed to cause a redistribution of circulating lymphoid subpopulations with subsequent reduction of normal T-suppressor lymphocytes and increased anti-tumour activity [ 17 , 18 ]. Thirdly, a radiation-induced release of cytokines, such as TNFα or IL-2, is believed to potentially stimulate a secondary immune modulation, enhancing anti-neoplastic cell-mediated effects [ 19 ]. In this context, another radiation-induced cell killing mechanism to be considered is the so-called "bystander effect", well described in several experimental studies and anecdotal clinical findings: this phenomenon consists of a biological response of unirradiated neighbours or distant cells after target cells irradiation.…”