Revising the Landscape of Cytokine-Induced Killer Cell Therapy in Lung Cancer: Focus on Immune Checkpoint Inhibitors

Abstract

Undeniably, immunotherapy has markedly improved the survival rate of cancer patients. The scenario is no different in lung cancer, where multiple treatment options are now available and the inclusion of immunotherapy yields better clinical benefits than previously used chemotherapeutic strategies. Of interest, cytokine-induced killer (CIK) cell immunotherapy has also taken a central role in clinical trials for the treatment of lung cancer. Herein, we describe the relative success of CIK cell therapy (alone and combined with dendritic cells as DC/CIKs) in lung cancer clinical trials and discuss its combination with known immune checkpoint inhibitors (anti-CTLA-4 and anti-PD-1/PD-L1). Additionally, we provide insights into the findings of several preclinical in vitro/in vivo studies linked to lung cancer. In our opinion, CIK cell therapy, which recently completed 30 years and has been approved in many countries, including Germany, offers tremendous potential for lung cancer. Foremost, when it is optimized on a patient-by-patient basis with special attention to the patient-specific genomic signature.

New insights into immune cells in cancer immunotherapy: from epigenetic modification, metabolic modulation to cell communication

“…For instance, CIK cellular immunotherapy provides a pivotal role in clinical trials for the treatment of cancer. 296 The CIK cell therapy combination with DCs has been relatively successful in lung cancer clinical trials. 297 , 298 Combination therapy with CIK cells and PD1 blocking antibodies showed potential for profound durable responses in NSCLC.…”

“…And these immunotherapeutic treatments have achieved a certain degree of effectiveness. For instance, CIK cellular immunotherapy provides a pivotal role in clinical trials for the treatment of cancer 296 . The CIK cell therapy combination with DCs has been relatively successful in lung cancer clinical trials 297,298 .…”

Multi‑omics approach to improve patient‑tailored therapy using immune checkpoint blockade and cytokine‑induced killer cell infusion in an elderly patient with lung cancer: A case report and literature review

“…After two courses of sintilimab treatment, SD was achieved; however, the symptoms, including cancer-associated pain, fatigue, malaise, a loss of appetite and poor mental state were not significantly improved. CIK cells have been suggested to improve the quality of life and enhance the effect of anti-PD-1 immunotherapy ( 28 ). Therefore, CIK cell infusions (1–2×10 9 cells/day for 3 consecutive days in each session, once per month and ≥3 days away from the treatment of PD-1 blockade) were added in combination with sintilimab to the subsequent courses of treatment.…”

Research progress on the immune microenvironment and immunotherapy in gastric cancer

“…A prospective study of 63 patients with advanced GC showed that the combination of dendritic cell-CIK with S-1 plus cisplatin resulted in promising PFS and OS (70). Furthermore, the adverse effects and toxicity of CIK cell treatment are moderate and easy to control (69,71). NK cells are activated as anti-tumor agents via the loss or downregulation of major histocompatibility complex I molecules, through which tumor cells can escape CTL recognition (72).…”