Inducing quiescent dormancy with conventional chemotherapy makes cancer cells more susceptible to immunotherapy, thereby minimizing potential for tumor recurrence, according to a study published in the Journal of Leukocyte Biology.1
Chemotherapy alone does not kill all cancer cells. Residual cells can become dormant cancer cells — indolent or quiescent type — that escape eradication and become resistant to further chemotherapy treatments. In addition, effectiveness of immunotherapy is hindered by tumor-induced immune suppression mediated by myeloid-derived suppressor cells and poor immunogenicity of the tumor-expressing self-antigens.
“Immunotherapy is all about timing. The best way to apply immunotherapy as cancer prevention is during tumor dormancy to prevent advanced stage disease,” explained Masoud H. Manjili, a researcher involved in the VCU study.2
In this study, researchers from the Department of Microbiology and Immunology, VCU School of Medicine, Richmond, Virginia, sought to induce dormancy in cancer cells, thereby making them more susceptible to immunotherapy.
The researchers treated breast cancer cells with doxorubicin, which killed most of the cancer cells. A residual population of cells not killed with the chemotherapy was determined to consist of indolent and dormant (quiescent) cells. Next, the researchers treated the breast cancer with immunotherapy. Their results showed that the dormant cells were susceptible to immunotherapy.
Their results show that administration of immunotherapy after chemotherapy can effectively target dormant cancer cells left after conventional chemotherapy before distant metastases occur, preventing advanced stage disease. However, administration of immunotherapy during active cancer cell proliferation can lead to immunoediting and immunologic escape during cell division.
“The challenge is to develop combinatorial therapies, ie, [adoptive immunotherapy], following the administration of epigenetic modulators or small molecules that could induce cell-cycle arrest and establish a quiescent type of tumor dormancy so as to render dormant tumor cells resistant to immunoediting and escape from immunotherapy,” the authors wrote.1
1. Payne KK, Keim RC, Graham L, et al. Tumor-reactive immune cells protect against metastatic tumor and induce immunoediting of indolent but not quiescent tumor cells. J Leukoc Biol. 2016;100(3):625-635.
2. Federation of American Societies for Experimental Biology. Researchers take step toward eliminating cancer recurrence. EurekAlert! web site. http://www.eurekalert.org/pub_releases/2016-09/foas-rts090116.php. Published September 1, 2016. Accessed September 12, 2016.