Estrogen Receptor Mutations As Novel Targets for Immunotherapy in Metastatic Estrogen Receptor-positive Breast Cancer

Overview

Journal Cancer Res Commun

Specialty Oncology

Date 2024 Feb 9

PMID 38335301

Authors

Jonathan Goldberg

Na Qiao

Jennifer L Guerriero

Brett Gross

Yagiz Meneksedag

Yoshimi F Lu

Anne V Philips

Tasnim Rahman

Funda Meric-Bernstam

Jason Roszik

Ken Chen

Rinath Jeselsohn

Sara M Tolaney

George E Peoples

Gheath Alatrash

Elizabeth A Mittendorf

Affiliations

Soon will be listed here.

Abstract

Significance: Estrogen receptor (ESR1) mutations have emerged as a key factor in endocrine therapy resistance. We identified and validated five novel, immunogenic ESR1-derived peptides that could be targeted through vaccine-based immunotherapy.

Citing Articles

Exploring the role of ESR1 mutations in metastatic hormone receptor-positive breast cancer T cell immune surveillance disruption.

Lopez M, Spehner L, Andre F, Viot J, Seffar E, Marguier A Breast Cancer Res. 2025; 27(1):19.

PMID: 39920833 PMC: 11806781. DOI: 10.1186/s13058-025-01962-6.

Breast cancer genomic analyses reveal genes, mutations, and signaling networks.

Manjunath G, Sharma S, Nashier D, Vasanthaiah S, Jha S, Bage S Funct Integr Genomics. 2024; 24(6):206.

PMID: 39496981 DOI: 10.1007/s10142-024-01484-y.

Association of GATA3 expression in triple-positive breast cancer with overall survival and immune cell infiltration.

Chen X, Zhao W, Huang Y, Luo S, Tang X, Yi Q Sci Rep. 2024; 14(1):17795.

PMID: 39090342 PMC: 11294334. DOI: 10.1038/s41598-024-68788-8.

References

Jeselsohn R, Buchwalter G, De Angelis C, Brown M, Schiff R . ESR1 mutations—a mechanism for acquired endocrine resistance in breast cancer. Nat Rev Clin Oncol. 2015; 12(10):573-83. PMC: 4911210. DOI: 10.1038/nrclinonc.2015.117. View

Khan M, Carmona S, Sukhumalchandra P, Roszik J, Philips A, Perakis A . Cathepsin G Is Expressed by Acute Lymphoblastic Leukemia and Is a Potential Immunotherapeutic Target. Front Immunol. 2018; 8:1975. PMC: 5790053. DOI: 10.3389/fimmu.2017.01975. View

Schwartzentruber D, Lawson D, Richards J, Conry R, Miller D, Treisman J . gp100 peptide vaccine and interleukin-2 in patients with advanced melanoma. N Engl J Med. 2011; 364(22):2119-27. PMC: 3517182. DOI: 10.1056/NEJMoa1012863. View

Blaha D, Anderson S, Yoakum D, Hager M, Zha Y, Gajewski T . High-Throughput Stability Screening of Neoantigen/HLA Complexes Improves Immunogenicity Predictions. Cancer Immunol Res. 2018; 7(1):50-61. PMC: 6324732. DOI: 10.1158/2326-6066.CIR-18-0395. View

Richters M, Xia H, Campbell K, Gillanders W, Griffith O, Griffith M . Best practices for bioinformatic characterization of neoantigens for clinical utility. Genome Med. 2019; 11(1):56. PMC: 6714459. DOI: 10.1186/s13073-019-0666-2. View

Fisk B, Blevins T, Wharton J, Ioannides C . Identification of an immunodominant peptide of HER-2/neu protooncogene recognized by ovarian tumor-specific cytotoxic T lymphocyte lines. J Exp Med. 1995; 181(6):2109-17. PMC: 2192068. DOI: 10.1084/jem.181.6.2109. View

Jeselsohn R, Bergholz J, Pun M, Cornwell M, Liu W, Nardone A . Allele-Specific Chromatin Recruitment and Therapeutic Vulnerabilities of ESR1 Activating Mutations. Cancer Cell. 2018; 33(2):173-186.e5. PMC: 5813700. DOI: 10.1016/j.ccell.2018.01.004. View

Katzenellenbogen J, Mayne C, Katzenellenbogen B, Greene G, Chandarlapaty S . Structural underpinnings of oestrogen receptor mutations in endocrine therapy resistance. Nat Rev Cancer. 2018; 18(6):377-388. PMC: 6252060. DOI: 10.1038/s41568-018-0001-z. View

Chen W, Colditz G . Risk factors and hormone-receptor status: epidemiology, risk-prediction models and treatment implications for breast cancer. Nat Clin Pract Oncol. 2007; 4(7):415-23. DOI: 10.1038/ncponc0851. View

10.

Croft N, Smith S, Pickering J, Sidney J, Peters B, Faridi P . Most viral peptides displayed by class I MHC on infected cells are immunogenic. Proc Natl Acad Sci U S A. 2019; 116(8):3112-3117. PMC: 6386720. DOI: 10.1073/pnas.1815239116. View

11.

Alatrash G, Perakis A, Kerros C, Peters H, Sukhumalchandra P, Zhang M . Targeting the Leukemia Antigen PR1 with Immunotherapy for the Treatment of Multiple Myeloma. Clin Cancer Res. 2018; 24(14):3386-3396. DOI: 10.1158/1078-0432.CCR-17-2626. View

12.

Zhou S, Liu S, Zhao L, Sun H . A Comprehensive Survey of Genomic Mutations in Breast Cancer Reveals Recurrent Neoantigens as Potential Therapeutic Targets. Front Oncol. 2022; 12:786438. PMC: 8978336. DOI: 10.3389/fonc.2022.786438. View

13.

Snyder A, Makarov V, Merghoub T, Yuan J, Zaretsky J, Desrichard A . Genetic basis for clinical response to CTLA-4 blockade in melanoma. N Engl J Med. 2014; 371(23):2189-2199. PMC: 4315319. DOI: 10.1056/NEJMoa1406498. View

14.

Qazilbash M, Wieder E, Thall P, Wang X, Rios R, Lu S . PR1 peptide vaccine induces specific immunity with clinical responses in myeloid malignancies. Leukemia. 2016; 31(3):697-704. PMC: 5332281. DOI: 10.1038/leu.2016.254. View

15.

Rizvi N, Hellmann M, Snyder A, Kvistborg P, Makarov V, Havel J . Cancer immunology. Mutational landscape determines sensitivity to PD-1 blockade in non-small cell lung cancer. Science. 2015; 348(6230):124-8. PMC: 4993154. DOI: 10.1126/science.aaa1348. View

16.

Fridman A, Finnefrock A, Peruzzi D, Pak I, La Monica N, Bagchi A . An efficient T-cell epitope discovery strategy using in silico prediction and the iTopia assay platform. Oncoimmunology. 2012; 1(8):1258-1270. PMC: 3518498. DOI: 10.4161/onci.21355. View

17.

Hosfield D, Weber S, Li N, Sauvage M, Joiner C, Hancock G . Stereospecific lasofoxifene derivatives reveal the interplay between estrogen receptor alpha stability and antagonistic activity in mutant breast cancer cells. Elife. 2022; 11. PMC: 9177151. DOI: 10.7554/eLife.72512. View

18.

Stronen E, Toebes M, Kelderman S, van Buuren M, Yang W, van Rooij N . Targeting of cancer neoantigens with donor-derived T cell receptor repertoires. Science. 2016; 352(6291):1337-41. DOI: 10.1126/science.aaf2288. View

19.

Dustin D, Gu G, Fuqua S . ESR1 mutations in breast cancer. Cancer. 2019; 125(21):3714-3728. PMC: 6788940. DOI: 10.1002/cncr.32345. View

20.

Murray J, Gillogly M, Przepiorka D, Brewer H, Ibrahim N, Booser D . Toxicity, immunogenicity, and induction of E75-specific tumor-lytic CTLs by HER-2 peptide E75 (369-377) combined with granulocyte macrophage colony-stimulating factor in HLA-A2+ patients with metastatic breast and ovarian cancer. Clin Cancer Res. 2002; 8(11):3407-18. View