Translating the Evolving Molecular Landscape of Tumors to Biomarkers of Response for Cancer Immunotherapy

Overview

Journal Sci Transl Med

Specialties General Medicine
Science

Date 2022 Nov 9

PMID 36350985

Authors

Valsamo Anagnostou

Blair V Landon

Jamie E Medina

Patrick Forde

Victor E Velculescu

Affiliations

Soon will be listed here.

Abstract

Immune checkpoint inhibitors (ICIs) have revolutionized cancer therapeutics, triggering studies to understand the molecular and cellular wiring of response and resistance. Our increased understanding of the underlying biology of response to ICI has enabled the investigation of tumor-intrinsic and -extrinsic features that may predict therapeutic outcomes. In parallel, liquid biopsy measurements of circulating tumor DNA (ctDNA) can be used to assess real-time molecular responses and guide clinical decisions during ICI. The combination of these approaches provides a deeper understanding of cancer biology, immunoediting, and evolution during ICI and promise to extend the utility of immunotherapies for patients with cancer.

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References

Tawbi H, Schadendorf D, Lipson E, Ascierto P, Matamala L, Castillo Gutierrez E . Relatlimab and Nivolumab versus Nivolumab in Untreated Advanced Melanoma. N Engl J Med. 2022; 386(1):24-34. PMC: 9844513. DOI: 10.1056/NEJMoa2109970. View

Larkin J, Chiarion-Sileni V, Gonzalez R, Grob J, Cowey C, Lao C . Combined Nivolumab and Ipilimumab or Monotherapy in Untreated Melanoma. N Engl J Med. 2015; 373(1):23-34. PMC: 5698905. DOI: 10.1056/NEJMoa1504030. View

Lahnemann D, Koster J, Szczurek E, McCarthy D, Hicks S, Robinson M . Eleven grand challenges in single-cell data science. Genome Biol. 2020; 21(1):31. PMC: 7007675. DOI: 10.1186/s13059-020-1926-6. View

Zhang Q, Luo J, Wu S, Si H, Gao C, Xu W . Prognostic and Predictive Impact of Circulating Tumor DNA in Patients with Advanced Cancers Treated with Immune Checkpoint Blockade. Cancer Discov. 2020; 10(12):1842-1853. PMC: 8358981. DOI: 10.1158/2159-8290.CD-20-0047. View

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

McGranahan N, Rosenthal R, Hiley C, Rowan A, Watkins T, Wilson G . Allele-Specific HLA Loss and Immune Escape in Lung Cancer Evolution. Cell. 2017; 171(6):1259-1271.e11. PMC: 5720478. DOI: 10.1016/j.cell.2017.10.001. View

Kortleve D, Coelho R, Hammerl D, Debets R . Cancer germline antigens and tumor-agnostic CD8 T cell evasion. Trends Immunol. 2022; 43(5):391-403. DOI: 10.1016/j.it.2022.03.006. View

Topalian S, Drake C, Pardoll D . Immune checkpoint blockade: a common denominator approach to cancer therapy. Cancer Cell. 2015; 27(4):450-61. PMC: 4400238. DOI: 10.1016/j.ccell.2015.03.001. View

Venkatesan S, Angelova M, Puttick C, Zhai H, Caswell D, Lu W . Induction of APOBEC3 Exacerbates DNA Replication Stress and Chromosomal Instability in Early Breast and Lung Cancer Evolution. Cancer Discov. 2021; 11(10):2456-2473. PMC: 8487921. DOI: 10.1158/2159-8290.CD-20-0725. View

10.

Willis J, Lefterova M, Artyomenko A, Kasi P, Nakamura Y, Mody K . Validation of Microsatellite Instability Detection Using a Comprehensive Plasma-Based Genotyping Panel. Clin Cancer Res. 2019; 25(23):7035-7045. DOI: 10.1158/1078-0432.CCR-19-1324. View

11.

Ayers M, Lunceford J, Nebozhyn M, Murphy E, Loboda A, Kaufman D . IFN-γ-related mRNA profile predicts clinical response to PD-1 blockade. J Clin Invest. 2017; 127(8):2930-2940. PMC: 5531419. DOI: 10.1172/JCI91190. View

12.

Skoulidis F, Goldberg M, Greenawalt D, Hellmann M, Awad M, Gainor J . Mutations and PD-1 Inhibitor Resistance in -Mutant Lung Adenocarcinoma. Cancer Discov. 2018; 8(7):822-835. PMC: 6030433. DOI: 10.1158/2159-8290.CD-18-0099. View

13.

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

14.

Passaro A, Brahmer J, Antonia S, Mok T, Peters S . Managing Resistance to Immune Checkpoint Inhibitors in Lung Cancer: Treatment and Novel Strategies. J Clin Oncol. 2022; 40(6):598-610. DOI: 10.1200/JCO.21.01845. View

15.

Van Allen E, Miao D, Schilling B, Shukla S, Blank C, Zimmer L . Genomic correlates of response to CTLA-4 blockade in metastatic melanoma. Science. 2015; 350(6257):207-211. PMC: 5054517. DOI: 10.1126/science.aad0095. View

16.

Caushi J, Zhang J, Ji Z, Vaghasia A, Zhang B, Hsiue E . Transcriptional programs of neoantigen-specific TIL in anti-PD-1-treated lung cancers. Nature. 2021; 596(7870):126-132. PMC: 8338555. DOI: 10.1038/s41586-021-03752-4. View

17.

Paz-Ares L, Ciuleanu T, Cobo M, Schenker M, Zurawski B, Menezes J . First-line nivolumab plus ipilimumab combined with two cycles of chemotherapy in patients with non-small-cell lung cancer (CheckMate 9LA): an international, randomised, open-label, phase 3 trial. Lancet Oncol. 2021; 22(2):198-211. DOI: 10.1016/S1470-2045(20)30641-0. View

18.

Marty R, Kaabinejadian S, Rossell D, Slifker M, van de Haar J, Engin H . MHC-I Genotype Restricts the Oncogenic Mutational Landscape. Cell. 2017; 171(6):1272-1283.e15. PMC: 5711564. DOI: 10.1016/j.cell.2017.09.050. View

19.

Herbst R, Baas P, Kim D, Felip E, Perez-Gracia J, Han J . Pembrolizumab versus docetaxel for previously treated, PD-L1-positive, advanced non-small-cell lung cancer (KEYNOTE-010): a randomised controlled trial. Lancet. 2015; 387(10027):1540-1550. DOI: 10.1016/S0140-6736(15)01281-7. View

20.

Yang W, Lee K, Srivastava R, Kuo F, Krishna C, Chowell D . Immunogenic neoantigens derived from gene fusions stimulate T cell responses. Nat Med. 2019; 25(5):767-775. PMC: 6558662. DOI: 10.1038/s41591-019-0434-2. View