These studies will examine how development of cancer can be affected by stressful conditions that are controllable in contrast to uncontrollable, and attempt to shed light on the mechanism by which stress can affect tumor development. The ability to exert control in a stressful situation is highly important for determining how stressful the situation is, being perhaps the most important behavioral/psychological influence on stress that has been discovered up to this time. For these studies, animal models and experimentally-induced tumors are employed: the proposed studies use the MADB 106 tumor that is syngeneic in Fisher 344 rats and the CC53 1 tumor that is syngeneic in WAG rats. The proposed project seeks to continue an ongoing collaboration between the laboratory of Dr. Jay Weiss, a behavioral/physiological psychologist and Professor of Psychiatry and Behavioral Sciences at Emory University, and that of Dr. Ronald Goldfarb, Director of the Institute for Cancer Research and Chairman of the Department of Molecular Biology and Immunology at the University of North Texas. Recent work of this collaborative group has revealed surprising new findings relating to regulation of the tumors indicated above. Earlier studies had shown that growth of these tumors was controlled by natural killer (NK) cells. Our recent findings, while confirming that NK cells are important in this regard, also indicate that B lymphocytes play an important role in this process. We found that B lymphocytes accumulate at the site of tumor development within a short time after tumor cells are introduced, and immunoneutralization studies indicate that actions of B lymphocytes occurring very soon after the tumor cells are present are important in defense against tumor development. Insofar as B lymphocytes are highly responsive to stressful conditions, stress effects on B lymphocytes may be an important aspect of how stress can affect cancer development. The proposed studies will determine the consequences of having control over a stressor vs. non-control on (1) lung tumor development using the models described above and (2) lymphocyte subtypes that accumulate at the site of tumor growth, and also (3) evaluate the possible role of B lymphocytes and circulating steroids in producing differences due to control vs. non-control. Further testing of the role of B lymphocytes in defense against tumor is done by examining (1) lymphocyte-tumor cell interaction using histological and electron microscopic techniques and (2) adoptive transfer of B lymphocytes. Finally, these approaches will be combined by assessing how control vs. non-control affects lymphocyte-tumor cell interaction assessed by histological analysis.
|Jones, Harlan P; Aldridge, Beau; Boss-Williams, Katherine et al. (2017) A role for B cells in facilitating defense against an NK cell-sensitive lung metastatic tumor is revealed by stress. J Neuroimmunol 313:99-108|