Induction of anti-leukemic responses by stimulation of leukemic CD3+ cells with allogeneic stimulator cells.

Autor: Pando A; Division of Hematology/Oncology, Rhode Island Hospital and the Warren Alpert School of Medicine at Brown University, One Hoppin Street, Coro West Suite 5.0.1, Providence, RI 02903 USA., Reagan JL; Division of Hematology/Oncology, Rhode Island Hospital and the Warren Alpert School of Medicine at Brown University, One Hoppin Street, Coro West Suite 5.0.1, Providence, RI 02903 USA., Nevola M; Division of Hematology/Oncology, Rhode Island Hospital and the Warren Alpert School of Medicine at Brown University, One Hoppin Street, Coro West Suite 5.0.1, Providence, RI 02903 USA., Fast LD; Division of Hematology/Oncology, Rhode Island Hospital and the Warren Alpert School of Medicine at Brown University, One Hoppin Street, Coro West Suite 5.0.1, Providence, RI 02903 USA.
Jazyk: angličtina
Zdroj: Experimental hematology & oncology [Exp Hematol Oncol] 2018 Oct 04; Vol. 7, pp. 25. Date of Electronic Publication: 2018 Oct 04 (Print Publication: 2018).
DOI: 10.1186/s40164-018-0118-5
Abstrakt: Background: Immunotherapeutic protocols have focused on identification of stimuli that induce effective anti-leukemic immune responses. One potent immune stimulus is the encounter with allogeneic cells. Our group previously showed that the infusion of haploidentical donor white blood cells (1-2 × 10 8 CD3+ cells/kg) into patients with refractory hematological malignancies induced responses of varying magnitude in over half of the patients. Because donor cells were eliminated within 2 weeks in these patients, it is presumed that the responses of recipient lymphocytes were critically important in achieving prolonged anti-leukemic responses.
Methods: The role of patient CD3+ cells in anti-leukemic responses was examined by isolating peripheral blood mononuclear cells from newly diagnosed leukemic patients. Immunophenotyping was performed on these peripheral blood mononuclear cells. CD3+ cells were isolated from the peripheral blood mononuclear cells and tested for their ability to proliferate and lyse autologous leukemic cells when stimulated with unrelated allogeneic cells.
Results: Allostimulated CD3+ cells effectively generated cytolytic responses to autologous CD3-cells in 11/21 patients. Increased numbers of CD4+ cells expressing high levels of granzyme A, B and perforin and CD8+CD39+ cells were found in nonresponsive CD3+ cells.
Conclusions: These results indicate that CD3+ cells from leukemic patients are capable of generating anti-leukemic responses when stimulated with unrelated allogeneic cells. This model can be used to identify approaches using alloreactive responses by patient lymphocytes to enhance in vivo anti-leukemic responses.
Databáze: MEDLINE
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