PD‑1 blockade enhances cytokine‑induced killer cell‑mediated cytotoxicity in B‑cell non‑Hodgkin lymphoma cell lines

Li, Yutao; Sharma, Amit; Bloemendal, Maurits W J R; Schmidt-Wolf, Roland; Kornek, Miroslaw; Schmidt‐Wolf, Ingo G.H.

doi:10.3892/ol.2021.12874

Cited by 11 publications

(8 citation statements)

References 17 publications

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“…CIK cell infusion, combined with DC (Dendritic cells), chemotherapy, or even immune checkpoint inhibitors are used clinically to treat various cancers and have obtained high clinical efficacy in lung cancer, hematologic tumor, and gastric cancer, etc. [ 2 – 6 ]. While CD3 + CD56 + T cells are recognized as a crucial effector population of CIK cells against tumor cells, the purification of CD56 + cell does not significantly improve the capacity in killing tumor cells compared with CIK cells [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

CD4+ T cells are required to improve the efficacy of CIK therapy in non-small cell lung cancer

et al. 2022

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As a widely studied adoptive treatment method, CIK (cytokine-induced killer cells) treatment has shown clinical benefits in many clinical trials on non-small cell lung cancer. As a heterogeneous cell population, however, CIK cells have a strong instability and individual differences in their efficacies, which are collaboratively regulated by the tumor microenvironment and CIK subpopulations. Among them, CD4+ T cells belong to a crucial subgroup of the CIK cell population, and their influence on CIK therapy is still unclear. Herein, we show how CD4+ T cells positively regulate the functions of CD3+CD56+ T and CD3+CD8+ T cells. During this process, we found that Th1/Th17 CD4+ subgroups can induce the phosphorylation of the AKT pathway by secreting IL-17A, and upregulate the expression of T-bet/Eomes transcription factors, thereby restoring the function of CD8+/CD3+CD56+ T cells and reversing the exhaustion of PD-1+Tim-3+ T cells. These findings will provide guidance for the clinical screening of suitable populations for CIK treatment and formulation of strategies for CIK therapy plus immune checkpoint treatment. Based on these findings, we are conducting an open-label phase II study (NCT04836728) is to evaluate the effects of autologous CIKs in combination with PD-1 inhibitor in the first-line treatment of IV NSCLC, and hope to observe patients’ benefits in this clinical trial.

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Section: Introductionmentioning

confidence: 99%

CD4+ T cells are required to improve the efficacy of CIK therapy in non-small cell lung cancer

et al. 2022

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“…Similarly, a critical role for the PD-1/PD-L costimulatory pathway in the alpha GalCer-mediated induction of iNKT cell anergy as a possible target for immunotherapies has been discussed [111]. Since PD-L1 expression is a predictive biomarker for CIK cell-based immunotherapy and the PD-1 blockade has been shown to enhance CIK cell cytotoxicity [112], the PD-Ls/NKT/CIK axis needs consideration. In order to delete the effect of Tregs on anti-tumor immunity, pre-administration of depleting anti-CD25 monoclonal antibodies prior to α-GalCer vaccination increased α-GalCer-induced prophylactic anti-tumor function in the GL261 murine glioma model, as mentioned above [106].…”

Section: Preclinical Nkt-mediated Immune Therapy In Glioblastomamentioning

confidence: 99%

Recent Development in NKT-Based Immunotherapy of Glioblastoma: From Bench to Bedside

Sharma

Maciaczyk

et al. 2022

IJMS

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Glioblastoma multiforme (GBM) is an aggressive and dismal disease with a median overall survival of around 15 months and a 5-year survival rate of 7.2%. Owing to genetic mutations, drug resistance, disruption to the blood–brain barrier (BBB)/blood–brain tumor barrier (BBTB), and the complexity of the immunosuppressive environment, the therapeutic approaches to GBM represent still major challenges. Conventional therapies, including surgery, radiotherapy, and standard chemotherapy with temozolomide, have not resulted in satisfactory improvements in the overall survival of GBM patients. Among cancer immunotherapeutic approaches, we propose that adjuvant NKT immunotherapy with invariant NKT (iNKT) and cytokine-induced killer (CIK) cells may improve the clinical scenario of this devastating disease. Considering this, herein, we discuss the current strategies of NKT therapy for GBM based primarily on in vitro/in vivo experiments, clinical trials, and the combinatorial approaches with future therapeutic potential.

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“…Biederbick et al recently contributed to raise concerns about synergistic molecular mechanisms of CIK cells by using a combination of anti-CD40 and anti-GITR mAb in the human lymphoma cell lines SU-DHL-4 and Daudi (both CD40-positive) [ 60 ]. More recently, Li et al reported an increase in IFN-γ secretion in B-NHL cell lines treated with CIK alone or with the PD-1 antibody, yet this trend was not observed for PD-L1, raising the question of whether PD-1 and PD-L1 are comparable and interchangeable in the clinical practice [ 61 ].…”

Section: Improving Cik Cell Therapy On Lymphomamentioning

confidence: 99%

Clinical Studies on Cytokine-Induced Killer Cells: Lessons from Lymphoma Trials

Zhang

Sharma

Weiher

et al. 2021

Cancers

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Cancer is a complex disease where resistance to therapies and relapses often pose a serious clinical challenge. The scenario is even more complicated when the cancer type itself is heterogeneous in nature, e.g., lymphoma, a cancer of the lymphocytes which constitutes more than 70 different subtypes. Indeed, the treatment options continue to expand in lymphomas. Herein, we provide insights into lymphoma-specific clinical trials based on cytokine-induced killer (CIK) cell therapy and other pre-clinical lymphoma models where CIK cells have been used along with other synergetic tumor-targeting immune modules to improve their therapeutic potential. From a broader perspective, we will highlight that CIK cell therapy has potential, and in this rapidly evolving landscape of cancer therapies its optimization (as a personalized therapeutic approach) will be beneficial in lymphomas.

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PD‑1 blockade enhances cytokine‑induced killer cell‑mediated cytotoxicity in B‑cell non‑Hodgkin lymphoma cell lines

Abstract: This work is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0) License.

Cited by 11 publications

References 17 publications

CD4+ T cells are required to improve the efficacy of CIK therapy in non-small cell lung cancer

CD4+ T cells are required to improve the efficacy of CIK therapy in non-small cell lung cancer

Recent Development in NKT-Based Immunotherapy of Glioblastoma: From Bench to Bedside

Clinical Studies on Cytokine-Induced Killer Cells: Lessons from Lymphoma Trials

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