CONICET | Buscador de Institutos y Recursos Humanos

The role of the immune system in the regression of mammarycarcinomas 􀀊􀀯C􀀋 using endocrine therapies has been poorly investigated.􀀹e have sho􀁙n that mifepristone 􀀊􀀯F􀀲, antiprogestin􀀋induces the regression of murine 􀀯C that express progesteronereceptors regardless of the immune system. Characterization ofthe immune cells in regressing tumors may provide clues relatedto their role in the prevention of tumor regro􀁙th. 􀀱ur aim 􀁙as tocharacterize the infiltrating cells in 􀀯F􀀲􀀏treated 􀀯C and to evaluate􀁙hether 􀀯F􀀲 􀁙as able to protect against tumor gro􀁙th in atumor re􀀏challenge assay after complete tumor resection. 􀀤onemarro􀁙 􀀊􀀤􀀯􀀋 cells from 􀀤AL􀀤/c􀀏􀀩F􀀲􀀍 mice 􀁙ere iv inoculatedinto immunodeficient 􀀰S􀀩 mice to establish the 􀀰S􀀩/􀀤􀀯􀀏􀀩F􀀲􀀍mouse model. 􀀗􀀛􀀏􀀔􀀏H􀀫 tumors, originated in 􀀤AL􀀤/c mice, 􀁙ereinoculated into 􀀰S􀀩 or 􀀰S􀀩/􀀤􀀯􀀏􀀩F􀀲􀀍 female mice. 􀀯F􀀲 pellets􀀊􀀒.􀀔 mg􀀋 􀁙ere implanted sc 􀁙hen the tumors reached 􀀗􀀒 mm2.Tumors 􀁙ere excised after 􀀕 or 􀀘 days and isolated cells analyzedby flo􀁙 cytometry. An increase in T lymphocytes 􀀊C􀀦􀀚􀀍􀀋and in macrophages 􀀊C􀀦􀀓􀀓b􀀍 F􀀖􀀚􀀒􀀍􀀝 p􀀞􀀒.􀀒􀀓􀀋, and a decreasein the Treg subpopulation 􀀊C􀀦􀀖􀀍 C􀀦􀀔􀀗􀀍 Foxp􀀕􀀍􀀝 p􀀞􀀒.􀀒􀀗􀀋, 􀁙as observedin 􀀯F􀀲􀀏treated tumors. 􀀫n the re􀀏challenge assay, tumors􀁙ere excised and pellets removed 􀀘 days after 􀀯F􀀲 treatment.Animals 􀁙ere orthotopically re􀀏inoculated 􀁙ith 􀀗􀀛􀀏􀀔􀀏H􀀫 tumors inthe opposite flan􀁍 􀀗 days after surgery. Sham operated animals􀁙ere used as controls. All secondary transplants gro􀁙ing inuntreated mice reached 200 mm2 before day 􀀖􀀙 􀁙hile only􀀗􀀒􀀇 of those mice previously treated 􀁙ith 􀀯F􀀲 reached thissize, p􀀞􀀒.􀀒􀀗. The reduced intratumor Treg/C􀀦􀀚􀀍 ratio observedin regressing tumors might be used as a predictive mar􀁍er oftreatment response. In sum, the data presented herein agree􀁙ith the hypothesis that regressing tumors expose intracellularantigens that generate a protective immune memory response,􀁙hich could be associated 􀁙ith the long free relapse survivalinduced by endocrine therapy.