Isoform specific anti-TGFβ therapy enhances antitumor efficacy in mouse models of cancer Journal Article


Authors: Gupta, A.; Budhu, S.; Fitzgerald, K.; Giese, R.; Michel, A. O.; Holland, A.; Campesato, L. F.; van Snick, J.; Uyttenhove, C.; Ritter, G.; Wolchok, J. D.; Merghoub, T.
Article Title: Isoform specific anti-TGFβ therapy enhances antitumor efficacy in mouse models of cancer
Abstract: TGFβ is a potential target in cancer treatment due to its dual role in tumorigenesis and homeostasis. However, the expression of TGFβ and its inhibition within the tumor microenvironment has mainly been investigated in stroma-heavy tumors. Using B16 mouse melanoma and CT26 colon carcinoma as models of stroma-poor tumors, we demonstrate that myeloid/dendritic cells are the main sources of TGFβ1 and TGFβ3. Depending on local expression of TGFβ isoforms, isoform specific inhibition of either TGFβ1 or TGFβ3 may be effective. The TGFβ signature of CT26 colon carcinoma is defined by TGFβ1 and TGFβ1 inhibition results in tumor delay; B16 melanoma has equal expression of both isoforms and inhibition of either TGFβ1 or TGFβ3 controls tumor growth. Using T cell functional assays, we show that the mechanism of tumor delay is through and dependent on enhanced CD8+ T cell function. To overcome the local immunosuppressive environment, we found that combining TGFβ inhibition with immune checkpoint blockade results in improved tumor control. Our data suggest that TGFβ inhibition in stroma poor tumors shifts the local immune environment to favor tumor suppression. © 2021, The Author(s).
Journal Title: Communications Biology
Volume: 4
Issue: 1
ISSN: 2399-3642
Publisher: Springer Nature  
Date Published: 2021-11-17
Start Page: 1296
Language: English
DOI: 10.1038/s42003-021-02773-z
PROVIDER: scopus
PMCID: PMC8599839
PUBMED: 34789823
DOI/URL:
Notes: Article -- Export Date: 1 December 2021 -- Source: Scopus
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MSK Authors
  1. Jedd D Wolchok
    905 Wolchok
  2. Taha Merghoub
    365 Merghoub
  3. Sadna Budhu
    86 Budhu
  4. Rachel Anne Giese
    14 Giese
  5. Aditi Gupta
    21 Gupta
  6. Adam Oliver Michel
    19 Michel
  7. Aliya Rose Ming Holland
    18 Holland