TY - JOUR
T1 - Engaging cytotoxic T and NK cells for immunotherapy in chronic lymphocytic leukemia
AU - Hofland, Tom
AU - Eldering, Eric
AU - Kater, Arnon P.
AU - Tonino, Sanne H.
PY - 2019/9/1
Y1 - 2019/9/1
N2 - Chronic lymphocytic leukemia (CLL) is characterized by an acquired immune dysfunction. CLL cells affect the phenotype and function of the entire spectrum of innate and adaptive immune cells, including monocytes, T cells, and natural killer (NK) cells, leading to a tumor-supportive environment and reduced immunosurveillance. Novel immunotherapies like immune checkpoint blockade, bi- and tri-specific antibodies, and chimeric antigen receptor (CAR) T cells use the patients’ immune system to induce therapeutic responses. Although these novel immunotherapies showed impressive results in several B cell lymphomas, responses in CLL were often disappointing. The strong immunomodulatory effect of CLL is believed to play a pivotal role in the low response rates to these immunotherapeutic strategies. In this review, we summarize how CLL influences the function of non-malignant lymphocytes, with a special focus on T and NK cells, two important cellular mediators for immunotherapy. Secondly, we provide a short overview of the activity of several immunotherapeutics in CLL, and discuss how novel strategies may overcome the disappointing response rates in CLL.
AB - Chronic lymphocytic leukemia (CLL) is characterized by an acquired immune dysfunction. CLL cells affect the phenotype and function of the entire spectrum of innate and adaptive immune cells, including monocytes, T cells, and natural killer (NK) cells, leading to a tumor-supportive environment and reduced immunosurveillance. Novel immunotherapies like immune checkpoint blockade, bi- and tri-specific antibodies, and chimeric antigen receptor (CAR) T cells use the patients’ immune system to induce therapeutic responses. Although these novel immunotherapies showed impressive results in several B cell lymphomas, responses in CLL were often disappointing. The strong immunomodulatory effect of CLL is believed to play a pivotal role in the low response rates to these immunotherapeutic strategies. In this review, we summarize how CLL influences the function of non-malignant lymphocytes, with a special focus on T and NK cells, two important cellular mediators for immunotherapy. Secondly, we provide a short overview of the activity of several immunotherapeutics in CLL, and discuss how novel strategies may overcome the disappointing response rates in CLL.
UR - https://www.scopus.com/inward/record.uri?partnerID=HzOxMe3b&scp=85071750334&origin=inward
UR - https://www.ncbi.nlm.nih.gov/pubmed/31484424
U2 - https://doi.org/10.3390/ijms20174315
DO - https://doi.org/10.3390/ijms20174315
M3 - Review article
C2 - 31484424
SN - 1422-0067
VL - 20
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
IS - 17
M1 - 4315
ER -