Quantifying PD-L1 Expression to Monitor Immune Checkpoint Therapy: Opportunities and Challenges

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2020 Nov 3

PMID 33137949

Citations 25

Authors

Sridhar Nimmagadda

Affiliations

Soon will be listed here.

Abstract

Therapeutics targeting programmed death ligand 1 (PD-L1) protein and its receptor PD-1 are now dominant players in restoring anti-tumor immune responses. PD-L1 detection by immunohistochemistry (IHC) is emerging as a reproducible biomarker for guiding patient stratification for those therapies in some cancers. However, PD-L1 expression in the tumor microenvironment is highly complex. It is upregulated by aberrant genetic alterations, and is highly regulated at the transcriptional, posttranscriptional, and protein levels. Thus, PD-L1 IHC is inadequate to fully understand the relevance of PD-L1 levels in the whole body and their dynamics to improve therapeutic outcomes. Imaging technologies could potentially assist in meeting that need. Early clinical investigations show promising results in quantifying PD-L1 expression in the whole body by positron emission tomography (PET). Within this context, this review summarizes advancements in regulation of PD-L1 expression and imaging agents, and in PD-L1 PET for drug development, and discusses opportunities and challenges presented by these innovations for guiding immune checkpoint therapy (ICT).

Citing Articles

Biomarkers for Immunotherapy Efficacy in Advanced Hepatocellular Carcinoma: A Comprehensive Review.

Taherifard E, Tran K, Saeed A, Yasin J, Saeed A Diagnostics (Basel). 2024; 14(18).

PMID: 39335733 PMC: 11431712. DOI: 10.3390/diagnostics14182054.

Navigating the landscape of PD-1/PD-L1 imaging tracers: from challenges to opportunities.

Badenhorst M, Windhorst A, Beaino W Front Med (Lausanne). 2024; 11:1401515.

PMID: 38915766 PMC: 11195831. DOI: 10.3389/fmed.2024.1401515.

Predictions of PD-L1 Expression Based on CT Imaging Features in Lung Squamous Cell Carcinoma.

Yeo S, Yoon H, Kim I, Kim Y, Lee Y, Cha Y J Korean Soc Radiol. 2024; 85(2):394-408.

PMID: 38617847 PMC: 11009139. DOI: 10.3348/jksr.2023.0011.

PET imaging of PD-L1 with a small molecule radiotracer.

Zhao Y, Hsu J, Hu S, Cai W Eur J Nucl Med Mol Imaging. 2024; 51(6):1578-1581.

PMID: 38459976 PMC: 11042986. DOI: 10.1007/s00259-024-06663-4.

Circulating Tumor Cells: How Far Have We Come with Mining These Seeds of Metastasis?.

Radhakrishnan V, Kaifi J, Suvilesh K Cancers (Basel). 2024; 16(4).

PMID: 38398206 PMC: 10887304. DOI: 10.3390/cancers16040816.

References

Brahmer J, Tykodi S, Chow L, Hwu W, Topalian S, Hwu P . Safety and activity of anti-PD-L1 antibody in patients with advanced cancer. N Engl J Med. 2012; 366(26):2455-65. PMC: 3563263. DOI: 10.1056/NEJMoa1200694. View

Giesen D, Broer L, Lub-de Hooge M, Popova I, Howng B, Nguyen M . Probody Therapeutic Design of Zr-CX-072 Promotes Accumulation in PD-L1-Expressing Tumors Compared to Normal Murine Lymphoid Tissue. Clin Cancer Res. 2020; 26(15):3999-4009. DOI: 10.1158/1078-0432.CCR-19-3137. View

Moroz A, Lee C, Wang Y, Hsiao J, Sevillano N, Truillet C . A Preclinical Assessment of Zr-atezolizumab Identifies a Requirement for Carrier Added Formulations Not Observed with Zr-C4. Bioconjug Chem. 2018; 29(10):3476-3482. PMC: 6430562. DOI: 10.1021/acs.bioconjchem.8b00632. View

Green M, Rodig S, Juszczynski P, Ouyang J, Sinha P, ODonnell E . Constitutive AP-1 activity and EBV infection induce PD-L1 in Hodgkin lymphomas and posttransplant lymphoproliferative disorders: implications for targeted therapy. Clin Cancer Res. 2012; 18(6):1611-8. PMC: 3321508. DOI: 10.1158/1078-0432.CCR-11-1942. View

Kang J, Demaria S, Formenti S . Current clinical trials testing the combination of immunotherapy with radiotherapy. J Immunother Cancer. 2016; 4:51. PMC: 5028964. DOI: 10.1186/s40425-016-0156-7. View

Mariathasan S, Turley S, Nickles D, Castiglioni A, Yuen K, Wang Y . TGFβ attenuates tumour response to PD-L1 blockade by contributing to exclusion of T cells. Nature. 2018; 554(7693):544-548. PMC: 6028240. DOI: 10.1038/nature25501. View

Roach C, Zhang N, Corigliano E, Jansson M, Toland G, Ponto G . Development of a Companion Diagnostic PD-L1 Immunohistochemistry Assay for Pembrolizumab Therapy in Non-Small-cell Lung Cancer. Appl Immunohistochem Mol Morphol. 2016; 24(6):392-7. PMC: 4957959. DOI: 10.1097/PAI.0000000000000408. View

Necchi A, Anichini A, Raggi D, Briganti A, Massa S, Luciano R . Pembrolizumab as Neoadjuvant Therapy Before Radical Cystectomy in Patients With Muscle-Invasive Urothelial Bladder Carcinoma (PURE-01): An Open-Label, Single-Arm, Phase II Study. J Clin Oncol. 2018; 36(34):3353-3360. DOI: 10.1200/JCO.18.01148. View

Sumimoto H, Takano A, Teramoto K, Daigo Y . RAS-Mitogen-Activated Protein Kinase Signal Is Required for Enhanced PD-L1 Expression in Human Lung Cancers. PLoS One. 2016; 11(11):e0166626. PMC: 5112979. DOI: 10.1371/journal.pone.0166626. View

10.

Simoni Y, Becht E, Fehlings M, Loh C, Koo S, Teng K . Bystander CD8 T cells are abundant and phenotypically distinct in human tumour infiltrates. Nature. 2018; 557(7706):575-579. DOI: 10.1038/s41586-018-0130-2. View

11.

Marzec M, Zhang Q, Goradia A, Raghunath P, Liu X, Paessler M . Oncogenic kinase NPM/ALK induces through STAT3 expression of immunosuppressive protein CD274 (PD-L1, B7-H1). Proc Natl Acad Sci U S A. 2008; 105(52):20852-7. PMC: 2634900. DOI: 10.1073/pnas.0810958105. View

12.

Jagoda E, Vasalatiy O, Basuli F, Opina A, Williams M, Wong K . Immuno-PET Imaging of the Programmed Cell Death-1 Ligand (PD-L1) Using a Zirconium-89 Labeled Therapeutic Antibody, Avelumab. Mol Imaging. 2019; 18:1536012119829986. PMC: 6498777. DOI: 10.1177/1536012119829986. View

13.

Dorand R, Nthale J, Myers J, Barkauskas D, Avril S, Chirieleison S . Cdk5 disruption attenuates tumor PD-L1 expression and promotes antitumor immunity. Science. 2016; 353(6297):399-403. PMC: 5051664. DOI: 10.1126/science.aae0477. View

14.

Pelengaris S, Khan M, Evan G . c-MYC: more than just a matter of life and death. Nat Rev Cancer. 2002; 2(10):764-76. DOI: 10.1038/nrc904. View

15.

Martinez P, Peters S, Stammers T, Soria J . Immunotherapy for the First-Line Treatment of Patients with Metastatic Non-Small Cell Lung Cancer. Clin Cancer Res. 2019; 25(9):2691-2698. DOI: 10.1158/1078-0432.CCR-18-3904. View

16.

Antonia S, Villegas A, Daniel D, Vicente D, Murakami S, Hui R . Durvalumab after Chemoradiotherapy in Stage III Non-Small-Cell Lung Cancer. N Engl J Med. 2017; 377(20):1919-1929. DOI: 10.1056/NEJMoa1709937. View

17.

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

18.

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

19.

Twa D, Chan F, Ben-Neriah S, Woolcock B, Mottok A, Tan K . Genomic rearrangements involving programmed death ligands are recurrent in primary mediastinal large B-cell lymphoma. Blood. 2014; 123(13):2062-5. DOI: 10.1182/blood-2013-10-535443. View

20.

Gniadek T, Li Q, Tully E, Chatterjee S, Nimmagadda S, Gabrielson E . Heterogeneous expression of PD-L1 in pulmonary squamous cell carcinoma and adenocarcinoma: implications for assessment by small biopsy. Mod Pathol. 2017; 30(4):530-538. DOI: 10.1038/modpathol.2016.213. View