Allergic pulmonary inflammation accelerates breast cancer metastasis via increase of myeloid cells in the lung microenvironment (TUM6P.1005)

Inflammation is known to contribute to tumor initiation and metastasis. Since it is not known the effect of pre-existing inflammation on metastasis, we combined a model of allergic pulmonary inflammation with a breast cancer model. Using this model, we found that allergen sensitized mice implanted with mammary tumors had a 5-fold increase in metastatic foci. More importantly allergic tumor bearing mice showed 3X faster tumor cell infiltration in their lungs with accelerated tumor growth and shorter survival. Since macrophages and MDSCs play a key role in the immunosuppressive processes associated with both inflammation and metastasis, we hypothesized that allergic pulmonary inflammatory microenvironment attracts myeloid cells that support incoming tumors cells and accelerates metastasis. We found an increase in the alveolar MO (CD11b - CD11C + CD68 + F4/80+Ly6G - ), interstitial MO (CD11b + CD11C - CD68 + F4/80 + Ly6G - ), monocytic MDSC (CD11b + Ly6C high Ly6G - F4/80 - ), and granulocytic MDSC (CD11b + Ly6C low Ly6G + F4/80 - ) subpopulations in mice with allergic pulmonary inflammation prior to tumor inoculation. These populations were further increased after tumor cell inoculation with the exception the granulocytic MDSCs. Depletion of macrophages and MDSCs prior to tumor cell inoculation in allergen mice decreased tumor growth and metastasis in allergic tumor bearing mice. Targeting specific immune populations could lead to safer and more efficient strategies against breast cancer metastasis.