Student or educator? Sign up with your school email and get 6 months of Pro free.
CoChat
Sign Up
Cited by 1,231

The DOI matches its Crossref record; 15 of the 15 references it cites were found in a registry or an index.

Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors

Open access
Akbay, Esra A., Koyama, Shohei, Carretero, Julian, Altabef, Abigail, Tchaicha, Jeremy H., Christensen, Camilla L., Mikse, Oliver R., Cherniack, Andrew D., Beauchamp, Ellen M., Pugh, Trevor J., Wilkerson, Matthew D., Fecci, Peter E., Butaney, Mohit, Reibel, Jacob B., Soucheray, Margaret, Cohoon, Travis J., Janne, Pasi A., Meyerson, Matthew, Hayes, D. Neil, Shapiro, Geoffrey I., Shimamura, Takeshi, Sholl, Lynette M., Rodig, Scott J., Freeman, Gordon J., Hammerman, Peter S., Dranoff, Glenn, Wong, Kwok-Kin·2013·Cancer Discovery
DOI 10.1158/2159-8290.cd-13-0310

Published version of a preprint

Open this paper in CoChat — free account

Abstract

The success in lung cancer therapy with programmed death (PD)-1 blockade suggests that immune escape mechanisms contribute to lung tumor pathogenesis. We identified a correlation between EGF receptor (EGFR) pathway activation and a signature of immunosuppression manifested by upregulation of PD-1, PD-L1, CTL antigen-4 (CTLA-4), and multiple tumor-promoting inflammatory cytokines. We observed decreased CTLs and increased markers of T-cell exhaustion in mouse models of EGFR-driven lung cancer. PD-1 antibody blockade improved the survival of mice with EGFR-driven adenocarcinomas by enhancing effector T-cell function and lowering the levels of tumor-promoting cytokines. Expression of mutant EGFR in bronchial epithelial cells induced PD-L1, and PD-L1 expression was reduced by EGFR inhibitors in non–small cell lung cancer cell lines with activated EGFR. These data suggest that oncogenic EGFR signaling remodels the tumor microenvironment to trigger immune escape and mechanistically link treatment response to PD-1 inhibition. Significance: We show that autochthonous EGFR-driven lung tumors inhibit antitumor immunity by activating the PD-1/PD-L1 pathway to suppress T-cell function and increase levels of proinflammatory cytokines. These findings indicate that EGFR functions as an oncogene through non–cell-autonomous mechanisms and raise the possibility that other oncogenes may drive immune escape. Cancer Discov; 3(12); 1355–63. ©2013 AACR. See related commentary by Rech and Vonderheide, p. 1330 This article is highlighted in the In This Issue feature, p. 1317

Overview

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 · 10.1158/2159-8290.cd-13-0310

Cites

15 of 15 references verified0 citation errors · 0 not checkable

Statistics

Verification

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

Self-check

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

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

Citations

Cites

Show all 15 references

Research works printed but not linked: 22

  1. Dunn, 2002, Cancer immunoediting: from immunosurveillance to tumor escape, Nat Immunol, 3, 991, 10.1038/ni1102-991 · DOI · Paper page
  2. Sharpe, 2007, The function of programmed cell death 1 and its ligands in regulating autoimmunity and infection, Nat Immunol, 8, 239, 10.1038/ni1443 · DOI · Paper page
  3. Parsa, 2007, Loss of tumor suppressor PTEN function increases B7-H1 expression and immunoresistance in glioma, Nat Med, 13, 84, 10.1038/nm1517 · DOI · Paper page
  4. Zaiss, 2013, Amphiregulin enhances regulatory T cell-suppressive function via the epidermal growth factor receptor, Immunity, 38, 275, 10.1016/j.immuni.2012.09.023 · DOI · Paper page
  5. Pivarcsi, 2007, Tumor immune escape by the loss of homeostatic chemokine expression, Proc Natl Acad Sci U S A, 104, 19055, 10.1073/pnas.0705673104 · DOI
  6. Ji, 2006, The impact of human EGFR kinase domain mutations on lung tumorigenesis and in vivo sensitivity to EGFR-targeted therapies, Cancer Cell, 9, 485, 10.1016/j.ccr.2006.04.022 · DOI · Paper page
  7. Li, 2007, Bronchial and peripheral murine lung carcinomas induced by T790M-L858R mutant EGFR respond to HKI-272 and rapamycin combination therapy, Cancer Cell, 12, 81, 10.1016/j.ccr.2007.06.005 · DOI · Paper page
  8. Chen, 2010, Inhibition of ALK, PI3K/MEK, and HSP90 in murine lung adenocarcinoma induced by EML4-ALK fusion oncogene, Cancer Res, 70, 9827, 10.1158/0008-5472.CAN-10-1671 · DOI · Paper page
  9. Weaver, 2012, Temporal molecular and biological assessment of an erlotinib-resistant lung adenocarcinoma model reveals markers of tumor progression and treatment response, Cancer Res, 72, 5921, 10.1158/0008-5472.CAN-12-0736 · DOI
  10. Francisco, 2010, The PD-1 pathway in tolerance and autoimmunity, Immunol Rev, 236, 219, 10.1111/j.1600-065X.2010.00923.x · DOI · Paper page
  11. Huang, 2009, PD-1 expression by macrophages plays a pathologic role in altering microbial clearance and the innate inflammatory response to sepsis, Proc Natl Acad Sci U S A, 106, 6303, 10.1073/pnas.0809422106 · DOI · Paper page
  12. Francisco, 2009, PD-L1 regulates the development, maintenance, and function of induced regulatory T cells, J Exp Med, 206, 3015, 10.1084/jem.20090847 · DOI · Paper page
  13. Shedden, 2008, Gene expression-based survival prediction in lung adenocarcinoma: a multi-site, blinded validation study, Nat Med, 14, 822, 10.1038/nm.1790 · DOI · Paper page
  14. Yonesaka, 2008, Autocrine production of amphiregulin predicts sensitivity to both gefitinib and cetuximab in EGFR wild-type cancers, Clin Cancer Res, 14, 6963, 10.1158/1078-0432.CCR-08-0957 · DOI
  15. Matsushita, 2012, Cancer exome analysis reveals a T-cell–dependent mechanism of cancer immunoediting, Nature, 482, 400, 10.1038/nature10755 · DOI · Paper page
  16. Shang, 2012, Deciphering the key features of malignant tumor microenvironment for anti-cancer therapy, Cancer Microenviron, 5, 211, 10.1007/s12307-012-0108-9 · DOI
  17. Frampton, 2012, Interleukin-6–driven progranulin expression increases cholangiocarcinoma growth by an Akt-dependent mechanism, Gut, 61, 268, 10.1136/gutjnl-2011-300643 · DOI
  18. Kudo-Saito, 2009, Cancer metastasis is accelerated through immunosuppression during Snail-induced EMT of cancer cells, Cancer Cell, 15, 195, 10.1016/j.ccr.2009.01.023 · DOI · Paper page
  19. Akalay, 2013, Epithelial-to-mesenchymal transition and autophagy induction in breast carcinoma promote escape from T-cell–mediated lysis, Cancer Res, 73, 2418, 10.1158/0008-5472.CAN-12-2432 · DOI · Paper page
  20. Curran, 2010, PD-1 and CTLA-4 combination blockade expands infiltrating T cells and reduces regulatory T and myeloid cells within B16 melanoma tumors, Proc Natl Acad Sci U S A, 107, 4275, 10.1073/pnas.0915174107 · DOI · Paper page
  21. Barber, 2006, Restoring function in exhausted CD8 T cells during chronic viral infection, Nature, 439, 682, 10.1038/nature04444 · DOI · Paper page
  22. Chen, 2013, PD-L1 expression is characteristic of a subset of aggressive B-cell lymphomas and virus-associated malignancies, Clin Cancer Res, 19, 3462, 10.1158/1078-0432.CCR-13-0855 · DOI · Paper page

Cited by

See all 1,231

Metadata

Authors
Akbay, E. A., Koyama, S., Carretero, J., Altabef, A., Tchaicha, J. H., Christensen, C. L., Mikse, O. R., Cherniack, A. D., Beauchamp, E. M., Pugh, T. J., Wilkerson, M. D., Fecci, P. E., Butaney, M., Reibel, J. B., Soucheray, M., Cohoon, T. J., Janne, P. A., Meyerson, M., Hayes, D. N., Shapiro, G. I., Shimamura, T., Sholl, L. M., Rodig, S. J., Freeman, G. J., Hammerman, P. S., Dranoff, G., & Wong, K.-K.
Venue
Cancer Discovery
Publisher
American Association for Cancer Research (AACR)
Published
2013-12-01
Volume
3
Issue
12
Pages
1355-1363
ISSN
  • 2159-8274 (ISSN-L)
  • 2159-8290
DOI
10.1158/2159-8290.cd-13-0310
OpenAlex
W2123918574
Cited by
1,231
References
15
FWCI
37.79
Type
journal article
Language
en
Open access
hybrid

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

How to cite

Cite CoChat for the checks on this page, and the paper for its own findings.

This page
CoChat. (2026). Citation check: Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors. https://app.cochat.ai/papers/10.1158/2159-8290.cd-13-0310
The paper
Akbay, E. A., Koyama, S., Carretero, J., Altabef, A., Tchaicha, J. H., Christensen, C. L., Mikse, O. R., Cherniack, A. D., Beauchamp, E. M., Pugh, T. J., Wilkerson, M. D., Fecci, P. E., Butaney, M., Reibel, J. B., Soucheray, M., Cohoon, T. J., Janne, P. A., Meyerson, M., Hayes, D. N., . . . Wong, K.-K. (2013). Activation of the PD-1 Pathway Contributes to Immune Escape in EGFR-Driven Lung Tumors. Cancer Discovery. https://doi.org/10.1158/2159-8290.cd-13-0310

Data sources

Bibliographic data: Semantic Scholar, OpenAlex, Crossref.

Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).

Semantic Scholar’s data is described in: Kinney, R., et al. (2023). The Semantic Scholar Open Data Platform. arXiv:2301.10140.