Cited by 103Cancer Cells and MetastasisCancer Immunotherapy and BiomarkersTGF-β signaling in diseases

Targeting the Interplay between Epithelial-to-Mesenchymal-Transition and the Immune System for Effective Immunotherapy

Open access
Soundararajan, Rama, Fradette, Jared, Konen, Jessica, Moulder, Stacy, Zhang, Xiang, Gibbons, Don, Varadarajan, Navin, Wistuba, Ignacio +13 more·2019·Cancers

Abstract

Over the last decade, both early diagnosis and targeted therapy have improved the survival rates of many cancer patients. Most recently, immunotherapy has revolutionized the treatment options for cancers such as melanoma. Unfortunately, a significant portion of cancers (including lung and breast cancers) do not respond to immunotherapy, and many of them develop resistance to chemotherapy. Molecular characterization of non-responsive cancers suggest that an embryonic program known as epithelial-mesenchymal transition (EMT), which is mostly latent in adults, can be activated under selective pressures, rendering these cancers resistant to chemo- and immunotherapies. EMT can also drive tumor metastases, which in turn also suppress the cancer-fighting activity of cytotoxic T cells that traffic into the tumor, causing immunotherapy to fail. In this review, we compare and contrast immunotherapy treatment options of non-small cell lung cancer (NSCLC) and triple negative breast cancer (TNBC). We discuss why, despite breakthrough progress in immunotherapy, attaining predictable outcomes in the clinic is mostly an unsolved problem for these tumors. Although these two cancer types appear different based upon their tissues of origin and molecular classification, gene expression indicate that they possess many similarities. Patient tumors exhibit activation of EMT, and resulting stem cell properties in both these cancer types associate with metastasis and resistance to existing cancer therapies. In addition, the EMT transition in both these cancers plays a crucial role in immunosuppression, which exacerbates treatment resistance. To improve cancer-related survival we need to understand and circumvent, the mechanisms through which these tumors become therapy resistant. In this review, we discuss new information and complementary perspectives to inform combination treatment strategies to expand and improve the anti-tumor responses of currently available clinical immune checkpoint inhibitors.

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Integrity signals

Registry

Crossref · 10.3390/cancers11050714

Cites

139 of 139 references verified0 citation errors · 0 not checkable

Statistics

Claims the paper makes

The claims and statistics of this paper haven’t been checked yet.

Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.

A few free checks a day · papers already verified open instantly · results are public

Claims other papers make about this one

Each is checked against this paper’s own text: does it say what the citing paper says it does?

  • EMT enables carcinoma cells to exert local immunosuppression by repressing MHCI antigen presentation and antigen processing/presentation machinery, thereby suppressing CD8+ T cell and NK cytotoxic activities.

    “Of further therapeutic relevance, EMT enables carcinoma cells to exert local immunosuppression143,144. EMT confers repression of major histocompatibility complex class I (MHCI) antigen presentation by tumor cells, which is required for recognition by CD8+ T cells, and thus indirectly suppresses cytotoxic activities of CD8+ T cells and cytolytic activities of NK cells141,143–145.”

    From TGFβ biology in cancer progression and immunotherapy (2021) · cites this paper as [143]

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The self-check needs the paper’s full text.

Cites

Flagged first, then by citations

Cited by

Sorted by citations

Authors
Soundararajan, R., Fradette, J., Konen, J., Moulder, S., Zhang, X., Gibbons, D., Varadarajan, N., Wistuba, I., Tripathy, D., Bernatchez, C., Byers, L., Chang, J., Contreras, A., Lim, B., Parra, E., Roarty, E., Wang, J., Yang, F., Barton, M., Rosen, J., & Mani, S.
Affiliations
  • The University of Texas MD Anderson Cancer Center (US)
  • Baylor College of Medicine (US)
  • University of Houston (US)
  • Department of Breast Medical Oncology, The University of Texas MD Anderson Cancer Center, Houston, TX 77030, USA
  • The University of Texas Health Science Center at Houston (US)
Corresponding author
  • Rosen, Jeffrey
  • Mani, Sendurai
Venue
Cancers
Publisher
MDPI AG
Published
2019-05-24
Volume
11
Issue
5
Pages
714
ISSN
2072-6694 (ISSN-L)
OpenAlex
W2945884255
Cited by
103
References
139
Citations by year
2026: 2 · 2025: 5 · 2024: 11 · 2023: 10 · 2022: 22 · 2021: 25 · 2020: 24 · 2019: 4
FWCI
1.79
Type
journal article
Language
en
Open access
Locations
  • Cancers (publishedVersion, cc-by)
  • Europe PMC (PubMed Central) (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion)
Funders
  • National Institutes of Health (2R01CA155243, NIH R37 CA214609-01A1)
  • NIH/NCI CCSG (P30-CA01667)
  • NIH/NCI SPORE (P5-CA070907)
  • MD Andersen Cancer Center Physician Scientist Award (N/A)
  • LUNGevity Foundation (N/A)
  • philanthropic contributions to The University of Texas MD Anderson Cancer Center Lung Cancer Moonshot Program (N/A)
  • CPRIT-MIRA (RP160652-P3, RP160710, RP180712)
  • Rexanna’s Foundation for Fighting Lung Cancer (N/A)
  • UT Lung SPORE Career Enhancement Award (P50 CA070907)
  • NIH/NCI (R01CA200970)
  • National Science Foundation (15-597-1605817)
  • CPRIT-IIRA (RP170172)
  • Dana Helis Henry and Andrienne Helis Malvin Medical Research Foundation Grant (N/A)
  • National Cancer Institute - University of Texas MD Anderson Prostate Cancer SPORE Career Enhancement Program Award (P50 CA140388)
  • MD Anderson Institutional Research Grant (N/A)
  • CPRIT (RP180466)
  • MRA (509800)
Topics
  • Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
  • Health Sciences › Medicine › Oncology › Cancer Immunotherapy and Biomarkers
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › TGF-β signaling in diseases
Keywords
epithelial-mesenchymal transition, cancer immunotherapy, immune checkpoint inhibitors, treatment resistance, non-small cell lung cancer, triple-negative breast cancer, tumor immunosuppression, tumor microenvironment, metastasis, cancer stemness, combination therapy, chemoresistance

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review