Changes of Immune Cell Fractions in Patients Treated with Immune Checkpoint Inhibitors

Overview

Journal Cancers (Basel)

Publisher MDPI

Specialty Oncology

Date 2022 Jul 27

PMID 35884501

Authors

Hye Ryeon Kim

Jung Hun Kang

Sung Hyun Kim

Seung Tae Kim

Ilhwan Kim

Young Joo Min

Seong Hoon Shin

Sung Yong Oh

Gyeong-Won Lee

Ji Hyun Lee

Jun Ho Ji

Seok Jae Huh

Suee Lee

Affiliations

Soon will be listed here.

Abstract

Background: With the development of immunology, immune checkpoint inhibitors (ICIs) have been widely used in various cancer treatments. Although some patients can benefit from ICIs, other patients have no response to ICIs or suffer from hyperprogression. There has been no biomarker for predicting the efficacy of ICIs. Thus, the objective of this study was to find biomarkers for predicting the efficacy of ICIs using peripheral blood.

Methods: Adults patients planned to be treated with ICIs were enrolled in this study. Blood sampling was carried out before and after administration of ICIs. Changes of immune cell fraction were analyzed for each patient.

Results: Among 182 patients enrolled, immune cell analysis was performed for 90 patients. The objective response rate was 14.4% ( = 13/90). The median progression-free survival (PFS) was 6.0 months (95% CI: 3.1-8.9 months), and the median overall survival (OS) was 13.9 months (95% CI: 5.6-22.2 months). Significant benefits in ORR and OS were shown for patients with increased NKp46-/CD56+ NK cells ( = 0.033 and = 0.013, respectively). The PFS tended to be longer in these patients, although the difference was not statistically significant ( = 0.050).

Conclusion: Changes of immune cell fraction before and after administration of ICIs could be a novel biomarker for predicting the efficacy of immunotherapy.

Citing Articles

Changes in Peripheral Immune Cells after the Third Dose of SARS-CoV-2 mRNA-BNT162b2 Vaccine and Disease Outcomes in Cancer Patients Receiving Immune Checkpoint Inhibitors: A Prospective Analysis of the Vax-on-Third-Profile Study.

Nelli F, Signorelli C, Fabbri A, Giannarelli D, Virtuoso A, Giron Berrios J Cancers (Basel). 2023; 15(14).

PMID: 37509286 PMC: 10377319. DOI: 10.3390/cancers15143625.

References

Hodi F, ODay S, Mcdermott D, Weber R, Sosman J, Haanen J . Improved survival with ipilimumab in patients with metastatic melanoma. N Engl J Med. 2010; 363(8):711-23. PMC: 3549297. DOI: 10.1056/NEJMoa1003466. View

Iwai Y, Ishida M, Tanaka Y, Okazaki T, Honjo T, Minato N . Involvement of PD-L1 on tumor cells in the escape from host immune system and tumor immunotherapy by PD-L1 blockade. Proc Natl Acad Sci U S A. 2002; 99(19):12293-7. PMC: 129438. DOI: 10.1073/pnas.192461099. View

Teng M, Galon J, Fridman W, Smyth M . From mice to humans: developments in cancer immunoediting. J Clin Invest. 2015; 125(9):3338-46. PMC: 4588291. DOI: 10.1172/JCI80004. View

Schiller J, Harrington D, Belani C, Langer C, Sandler A, Krook J . Comparison of four chemotherapy regimens for advanced non-small-cell lung cancer. N Engl J Med. 2002; 346(2):92-8. DOI: 10.1056/NEJMoa011954. View

Zhao P, Li L, Jiang X, Li Q . Mismatch repair deficiency/microsatellite instability-high as a predictor for anti-PD-1/PD-L1 immunotherapy efficacy. J Hematol Oncol. 2019; 12(1):54. PMC: 6544911. DOI: 10.1186/s13045-019-0738-1. View

Reck M, Rodriguez-Abreu D, Robinson A, Hui R, Csoszi T, Fulop A . Pembrolizumab versus Chemotherapy for PD-L1-Positive Non-Small-Cell Lung Cancer. N Engl J Med. 2016; 375(19):1823-1833. DOI: 10.1056/NEJMoa1606774. View

Sasidharan Nair V, Elkord E . Immune checkpoint inhibitors in cancer therapy: a focus on T-regulatory cells. Immunol Cell Biol. 2018; 96(1):21-33. DOI: 10.1111/imcb.1003. View

Gadgeel S, Rodriguez-Abreu D, Speranza G, Esteban E, Felip E, Domine M . Updated Analysis From KEYNOTE-189: Pembrolizumab or Placebo Plus Pemetrexed and Platinum for Previously Untreated Metastatic Nonsquamous Non-Small-Cell Lung Cancer. J Clin Oncol. 2020; 38(14):1505-1517. DOI: 10.1200/JCO.19.03136. View

Bellmunt J, de Wit R, Vaughn D, Fradet Y, Lee J, Fong L . Pembrolizumab as Second-Line Therapy for Advanced Urothelial Carcinoma. N Engl J Med. 2017; 376(11):1015-1026. PMC: 5635424. DOI: 10.1056/NEJMoa1613683. View

10.

Pardoll D . The blockade of immune checkpoints in cancer immunotherapy. Nat Rev Cancer. 2012; 12(4):252-64. PMC: 4856023. DOI: 10.1038/nrc3239. View

11.

Muro K, Chung H, Shankaran V, Geva R, Catenacci D, Gupta S . Pembrolizumab for patients with PD-L1-positive advanced gastric cancer (KEYNOTE-012): a multicentre, open-label, phase 1b trial. Lancet Oncol. 2016; 17(6):717-726. DOI: 10.1016/S1470-2045(16)00175-3. View

12.

Darvin P, Toor S, Sasidharan Nair V, Elkord E . Immune checkpoint inhibitors: recent progress and potential biomarkers. Exp Mol Med. 2018; 50(12):1-11. PMC: 6292890. DOI: 10.1038/s12276-018-0191-1. View

13.

Hirsch F, McElhinny A, Stanforth D, Ranger-Moore J, Jansson M, Kulangara K . PD-L1 Immunohistochemistry Assays for Lung Cancer: Results from Phase 1 of the Blueprint PD-L1 IHC Assay Comparison Project. J Thorac Oncol. 2016; 12(2):208-222. DOI: 10.1016/j.jtho.2016.11.2228. View

14.

Rosenberg J, Hoffman-Censits J, Powles T, van der Heijden M, Balar A, Necchi A . Atezolizumab in patients with locally advanced and metastatic urothelial carcinoma who have progressed following treatment with platinum-based chemotherapy: a single-arm, multicentre, phase 2 trial. Lancet. 2016; 387(10031):1909-20. PMC: 5480242. DOI: 10.1016/S0140-6736(16)00561-4. View

15.

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

16.

Yarchoan M, Albacker L, Hopkins A, Montesion M, Murugesan K, Vithayathil T . PD-L1 expression and tumor mutational burden are independent biomarkers in most cancers. JCI Insight. 2019; 4(6). PMC: 6482991. DOI: 10.1172/jci.insight.126908. View

17.

Glasner A, Levi A, Enk J, Isaacson B, Viukov S, Orlanski S . NKp46 Receptor-Mediated Interferon-γ Production by Natural Killer Cells Increases Fibronectin 1 to Alter Tumor Architecture and Control Metastasis. Immunity. 2018; 48(1):107-119.e4. DOI: 10.1016/j.immuni.2017.12.007. View

18.

Buttner R, Longshore J, Lopez-Rios F, Merkelbach-Bruse S, Normanno N, Rouleau E . Implementing TMB measurement in clinical practice: considerations on assay requirements. ESMO Open. 2019; 4(1):e000442. PMC: 6350758. DOI: 10.1136/esmoopen-2018-000442. View

19.

Herbst R, Soria J, Kowanetz M, Fine G, Hamid O, Gordon M . Predictive correlates of response to the anti-PD-L1 antibody MPDL3280A in cancer patients. Nature. 2014; 515(7528):563-7. PMC: 4836193. DOI: 10.1038/nature14011. View

20.

Garon E, Rizvi N, Hui R, Leighl N, Balmanoukian A, Eder J . Pembrolizumab for the treatment of non-small-cell lung cancer. N Engl J Med. 2015; 372(21):2018-28. DOI: 10.1056/NEJMoa1501824. View