Mycobacterium Bovis Bacillus Calmette-Guerin (BCG) Alters Melanoma Microenvironment Favoring Antitumor T Cell Responses and Improving M2 Macrophage Function

LARDONE, RICARDO D; CHAN ALFRED; LEE AGNES F; FOSHAG L; FARIES, MARK; SIELING PETER; LEE DELPHINE

Frontiers in Immunology

Frontiers

Lugar: Laussane; Año: 2017 vol. 8

ntralesional Mycobacterium bovis Bacillus Calmette-Guérin (BCG) has long been a relatively inexpensive therapy for inoperable cutaneous metastatic melanoma (CMM), although intralesional BCG skin mechanisms remain understudied. We analyzed intralesional BCG-treated CMM lesions combined with in vitro studies to further investigate BCG-altered pathways. Since macrophages play a pivotal role against both cancer and mycobacterial infections, we hypothesized BCG regulates macrophages to promote antitumor immunity. Tumor-associated macrophages (M2) infiltrate melanomas and impair antitumor immunity. BCG-treated, in vitro-polarized M2 (M2-BCG) showed transcriptional changes involving inflammation, immune cell recruitment, cross-talk and activation pathways. Mechanistic network analysis indicated M2-BCG potential to improve IFN-γ responses. Accordingly, frequency of IFN-γ-producing CD4+ T cells responding to M2-BCG vs. mock-treated M2 increased (p