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Research Article Open access CC BY 4.0

Optimization of PD-1 / PD-L1 Blockade to Increase NK Cells Cytotoxicity in Killing Cancer Cells: Article Review

Joko Wibowo Sentoso, Agung Putra, Iffan Alif

Journal of Cancer and Tumor International · pp. 32–39 · Published 8 Apr 2024

10.9734/jcti/2024/v14i1248

Abstract

Anti-PD-1 and anti-PD-L1 are therapies that have shown success in cancer treatment. However, while treating cancer with PD-1/PD-L1 blockade is similar, the clinical response rate is still low in certain cancers at around 40%. Therefore, therapeutic strategies are needed to increase PD-L1 expression and optimize PD-1/PD-L1 blockade therapy, so as to improve satisfactory therapeutic results. In tumors, IFNγ induces the expression of PD-L1 which is a cytokine secreted by Natural Killer cells. A study showed that PM21-NK cells induced large amounts of IFNγ and transfected PM21-NK cells adaptively induced PD-L1 expression. In in vitro experiments, anti-PD-L1 treatment had no direct effect on cytotoxicity or cytokine secretion by PD-1 negative PM21-NK cells in response to PD-L1+ targets. However, in vivo a significant increase in the antitumor effect of Natural Killer cells was found when combined with anti-PD-L1. PD-L1 blockade also resulted in increased persistence of Natural Killer cells in vivo and retention of their cytotoxic phenotype. These results support the use of anti-PD-L1 in combination with Natural Killer cell therapy regardless of baseline tumor PD-L1 status and suggest that Natural Killer cell therapy will likely increase the applicability of anti-PD-L1 treatment. In this review article, the author will discuss the method of optimizing PD-L1 blockade combined with Natural Killer cell therapy to increase the efficacy of treatment on cancer stem cells in the dormant phase.

PD-1 PDL-1 natural killer cell cancer cells

References (22)

  1. 1 Role of the tumor microenvironment in PD-L1/PD-1-mediated tumor immune escape [DOI]
  2. 2 Mechanisms of natural killer cell-mediated cellular cytotoxicity [DOI]
  3. 3 Improvement of the anticancer efficacy of PD-1/PD-L1 blockade via combination therapy and PD-L1 regulation [DOI]
  4. 4 Identification of a subset of human natural killer cells expressing high levels of programmed death 1: A phenotypic and functional characterization [DOI]
  5. 5 Engineering Natural Killer Cells for Cancer Immunotherapy [DOI]
  6. 6 Differential Expression of PD-L1 between Primary and Metastatic Sites in Clear-Cell Renal Cell Carcinoma [DOI]
  7. 7 Immune evasion via PD-1/PD-L1 on NK cells and monocyte/macrophages is more prominent in Hodgkin lymphoma than DLBCL [DOI]
  8. 8 The Role of PD-1 in Acute and Chronic Infection [DOI]
  9. 9 PD-1 is a haploinsufficient suppressor of T cell lymphomagenesis [DOI]
  10. 10 The Role Of PD-1/PD-L1 Axis In Treg Development And Function: Implications For Cancer Immunotherapy [DOI]
  11. 11 PD-1 Increases PTEN Phosphatase Activity While Decreasing PTEN Protein Stability by Inhibiting Casein Kinase 2 [DOI]
  12. 12 PD/1-PD-Ls Checkpoint: Insight on the Potential Role of NK Cells [DOI]
  13. 13 Natural Killer Cell Education and the Response to Infection and Cancer Therapy: Stay Tuned [DOI]
  14. 14 PD-L1 blockade enhances anti-tumor efficacy of NK cells [DOI]
  15. 15 The PD‐1/PD‐L1 (B7‐H1) Pathway in Chronic Infection‐Induced Cytotoxic T Lymphocyte Exhaustion [DOI]
  16. 16 Avelumab, an IgG1 anti-PD-L1 Immune Checkpoint Inhibitor, Triggers NK Cell-Mediated Cytotoxicity and Cytokine Production Against Triple Negative Breast Cancer Cells [DOI]
  17. 17 Immunotherapy of cancers comes of age [DOI]
  18. 18 Cell-Extrinsic MHC Class I Molecule Engagement Augments Human NK Cell Education Programmed by Cell-Intrinsic MHC Class I [DOI]
  19. 19 Epigenetic priming of both tumor and NK cells augments antibody-dependent cellular cytotoxicity elicited by the anti-PD-L1 antibody avelumab against multiple carcinoma cell types [DOI]
  20. 20 Mechanisms of Primary and Secondary Resistance to Immune Checkpoint Inhibitors in Cancer [DOI]
  21. 21 Recognition of the Major Histocompatibility Complex (MHC) Class Ib Molecule H2-Q10 by the Natural Killer Cell Receptor Ly49C [DOI]
  22. 22 Prognostic Role of Immune Checkpoint Regulators in Cholangiocarcinoma: A Pilot Study [DOI]

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