Stress, NK cells, and cancer: Still a promissory note

Although the last decades have provided ample evidence for deleterious effects of stress on immunity and on cancer development and suggested mediating mechanisms, no psychoneuroimmunology (PNI)-related intervention has become a standard of care in conventional cancer treatment. We believe the reasons for this include the unique nature of cancer evolvement and interactions with the immune system, and the many conceptual and technical obstacles to studying stress effects on immune activity and their implications for human resistance to malignancy. However, the numerous and diverse interactions between malignant tissue and immunocytes are now better understood, and suggestions can be made with respect to certain critical periods to be investigated in cancer-PNI research. Animal models of cancer progression are instrumental in suggesting neuroendocrine and immunological mediators of stress effects on specific aspects of cancer progression, especially with respect to the role of NK cell activity. The ultimate clinical relevance, however, must be tested in cancer patients. Recent animal studies suggest a role for the sympathetic nervous system in mediating biologically relevant stress effects on immunity and on tumor progression. Related interventions can now be tested in patients to support or refute the promise of such studies.