Preliminary Investigation of the Role of Cellular Immunity in Estrous Cycle Modulation of Post-Resection Breast Cancer Spread

摘要

The timing of resection of a transplantable breast cancer within the mouse's estrous cycle affects whether the cancer metastasizes or whether the operation cures the mouse. Surgery during the pro-estrus phase cured 2 1/2 times more frequently than the opposite timing. The authors have studied the immune capacity of the mouse to generate natural killer (NK) cell activity. Surgical curability was optimal during pro-estrus when immunocompetence was most robust. Enhancing NK function diminishes metastatic spread while interfering with NK function increases spread. Estrogens diminish NK function. The authors plan to determine whether hormone-dependent immunocyte suppression affects fertility cycle modulation of cancer spread; which female sex hormones control post-resection spread; whether estrogen and/or progesterone affect the duration of NK cell activity suppression and numbers of NK, helper T, and/or suppressor T cells following resection; and whether deleting specific immune cell types by 'in vivo' administration of antibodies abrogates the estrous cycle and sex hormone modulation of post-resection cancer spread. Demonstration that NK, T helper, and/or T suppressor cells are essential for sex hormone modulation of cancer spread would implicate neo-adjuvant sex hormone and other cellular immune enhancement strategies before and/or following breast cancer resection to improve cure frequency.