Transcriptomics,Genomics

Dataset Information

167

Mycobacterium bovis Bacillus Calmette-Guerin (BCG) reprograms melanoma microenvironment to promote antitumor T cell responses


ABSTRACT: Intralesional therapy using Mycobacterium bovis Bacillus Calmette-Guérin (BCG) for cutaneous metastatic melanoma induces regression of injected, but also non-injected lesions. Tumor-associated macrophages (also known as M2) infiltrate solid tumors and impair antitumor immunity. Since macrophages play a pivotal role in both tumors and mycobacterial infections, we hypothesized BCG alters M2 to promote antitumor immunity. BCG-treated, in vitro-polarized M2 (M2-BCG) show dramatic transcriptional changes involving inflammation, immune cell recruitment, cross-talk and activation pathways. Mechanistic network analysis indicates potential for M2-BCG to improve IFN-γ responses, frequently used as a marker for successful antitumor immunity. Accordingly, we found an increased frequency of IFN-γ-producing CD4+ T cells responding to M2-BCG vs mock-treated M2 (p<0.05). Moreover, supernatant from M2-BCG increased the frequency of granzyme B-producing CD8+ tumor-infiltrating lymphocytes (TIL) responding to autologous melanoma cell lines (p<0.01). Comparing the transcriptome of injected vs uninjected lesions biopsied from IL-BCG patients showed immune function prevailing in injected lesions, with the most enriched pathways representing T cell activation mechanisms. In vitro BCG-infected tumor cells also stimulated IFN-γ production from HLA-A2-restricted syngeneic TIL from the same melanoma patient (p<0.05). Together, our data indicates BCG can promote an antitumor microenvironment in cutaneous metastatic melanoma.  Overall design: 15 samples in total. 3 groups: M1 with media, M2 with media, M2 with BCG (5 replicates for each group with patient pairing)

INSTRUMENT(S): Illumina HiSeq 2000 (Homo sapiens)

SUBMITTER: Delphine Lee  

PROVIDER: GSE90748 | GEO | 2017-09-14

SECONDARY ACCESSION(S): PRJNA355844

REPOSITORIES: GEO

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Publications

Mycobacterium bovis Bacillus Calmette-Guérin Alters Melanoma Microenvironment Favoring Antitumor T Cell Responses and Improving M2 Macrophage Function.

Lardone Ricardo D RD   Chan Alfred A AA   Lee Agnes F AF   Foshag Leland J LJ   Faries Mark B MB   Sieling Peter A PA   Lee Delphine J DJ  

Frontiers in immunology 20170811


Intralesional 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 antit  ...[more]

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