Acquisition of Ly49 Receptor Expression by Developing Natural Killer Cells

The formation of the repertoire of mouse natural killer (NK) cell receptors for major histocompatibility complex (MHC) class I molecules was investigated by determining the developmental pattern of Ly49 receptor expression. During the first days after birth, few or no splenic NK cells express Ly49A, Ly49C, Ly49G2, or Ly49I receptors. The proportion of Ly49+ splenic NK cells gradually rises to adult levels during the first 6–8 wk of life. The appearance of appreciable numbers of splenic Ly49+ NK cells coincides with the appearance of NK activity at 3–4 wk. After in vivo transfer, NK cells not expressing specific Ly49 receptors can give rise to NK cells that do, and cells expressing one of these four Ly49 receptors can give rise to cells expressing others. Once initiated, expression of a Ly49 receptor is stable for at least 10 d after in vivo transfer. Hence, initiation of Ly49 receptor expression occurs successively. Interestingly, expression of one of the receptors tested, Ly49A, did not occur after in vivo transfer of Ly49A− cells. One possible explanation for these data is that the order of Ly49 receptor expression by NK cells is nonrandom. The results provide a framework for evaluating models of NK cell repertoire formation, and how the repertoire is molded by host class I MHC molecules

Classification of current anticancer immunotherapies

During the past decades, anticancer immunotherapy has evolved from a promising therapeutic option to a robust clinical reality. Many immunotherapeutic regimens are now approved by the US Food and Drug Administration and the European Medicines Agency for use in cancer patients, and many others are being investigated as standalone therapeutic interventions or combined with conventional treatments in clinical studies. Immunotherapies may be subdivided into “passive” and “active” based on their ability to engage the host immune system against cancer. Since the anticancer activity of most passive immunotherapeutics (including tumor-targeting monoclonal antibodies) also relies on the host immune system, this classification does not properly reflect the complexity of the drug-host-tumor interaction. Alternatively, anticancer immunotherapeutics can be classified according to their antigen specificity. While some immunotherapies specifically target one (or a few) defined tumor-associated antigen(s), others operate in a relatively non-specific manner and boost natural or therapy-elicited anticancer immune responses of unknown and often broad specificity. Here, we propose a critical, integrated classification of anticancer immunotherapies and discuss the clinical relevance of these approaches