Cytokine-induced killer cells: new insights for therapy of hematologic malignancies

Sep 21, 2026

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Cytokine-induced killer (CIK) cells are an immune effector subgroup used for immunotherapy, combining MHC-unrestricted cytotoxicity against hematologic and solid malignancies with a low incidence of severe treatment complications. This review summarizes CIK-cell structure and rationale, highlighting improved proliferation, migration, invasiveness to tumor sites, and antitumor activity with a broader spectrum than previously reported antitumor immune cells. CIK-based approaches show efficacy in clinical trials with low GVHD risk, including MHC-mismatched and haploidentical transplantation settings, while remaining subject to ongoing controversy.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages21

Reading Time53 min

AccessFree to download

Background

Hematologic malignancies and clinical burden

Risk factors and diagnostic approaches

Cytokine-induced killer (CIK) cells

Cell composition and primary effectors

Key biological advantages versus other antitumor effectors

Mechanisms of tumor-cell death and clinical trial findings

Conclusion

Ghanbari Sevari et al. Stem Cell Research & Therapy (2024) 15:254 [https://doi.org/10.1186/s13287-024-03869-z](https://doi.org/10.1186/s13287-024-03869-z) Stem Cell Research & Therapy REVIEW Open Access Cytokine-induced killer cells: new insights for therapy of hematologic malignancies Faezeh Ghanbari Sevari1 , Amir Mehdizadeh1 , Khadijeh Abbasi2, Seyyed Sina Hejazian3,4* and Mortaza Raeisi 1* Abstract Background Cytokine-induced killer (CIK) cells are a novel subgroup of immune effectors, classified as oneof the modified T cell-mediated arms for immunotherapy. These cells exert MHC‐unrestricted cytotoxicity against both hematological and solid malignancies with low incidence of treatment‐related severe complications. This study reviews the application of CIK cells in treating cases with hematologic malignancies. Main body CIK cells consist of CD3+/CD56+ natural killer (NK) T cells, CD3 −/CD56+ NK cells, and CD3+/CD56 − cytotoxic T cells. In this regard, the CD3+/CD56+ NKT cells are the primary effectors. Compared with the previously reported antitumor immune cells, CIK cells are characterized by improved in vitro proliferation and amplification, enhanced migration and invasive capacity to tumor region, more significant antitumor activity, and a broader antitumor spectrum. CIK cells can also induce death in tumor cells via numerous pathways and mechanisms. Hence, CIKsbased therapy has been used in various clinical trials and has shown efficacy with a very low graft versus host disease (GVHD) against several cancers, such as hematologic malignancies, even in relapsing cases, or cases not responding to other therapies. Despite the high content ofT cells, CIK cells induce low alloreactivity and, thus, pose a restricted threat of GVHD induction even in MHC-mismatched transplantation cases. Phase 1 and 2 clinical trials of CIK cell therapy have also highlighted satisfactory therapeutic advantages against hematologic cancers, indicating the safety of CIK cells even in haploidentical transplantation settings. Conclusion CIK cells have shown promising results in the treatment of hematologic malignancies, especially in combination with other antitumor strategies. However, the existing controversies in achieving desired clinical responses underscore the importance of future studies. Keywords Hematologic malignancies, CIK cell, Therapy, Cancer *Correspondence: Seyyed Sina Hejazian [hejazians@tbzmed.ac.ir](hejazians@tbzmed.ac.ir); [sina.hej95@gmail.com](sina.hej95@gmail.com) Mortaza Raeisi[raiisy@yahoo.com](raiisy@yahoo.com) 1 Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 2 Department of Biochemistry and Clinical Laboratories, Faculty of Medicine, Tabriz University of Medical Sciences, Tabriz, Iran 3 Neuroscience Research Center, Tabriz University of Medical Sciences, Tabriz, Iran 4 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran Background Hematological malignancies are a specific category of tumors that impact the normal function of blood cells, bone marrow, and lymph nodes [1]. In this regard, several well-researched hematopoietic cancers are leukemia, non-Hodgkin lymphoma (NHL), Hodgkin lymphoma (HL), multiple myeloma (MM), myelodysplastic syndromes (MDS) and myeloproliferative disorders [2, 3]. In addition to other blood disorders, hematologic cancers drastically increase worldwide death and morbidity rates [4]. These malignancies are the fifth most prevalent form of cancer and the 2nd highest etiology of cancer-induced © The Author(s) 2024. Open Access This article is licensed under a Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International License, which permits any non-commercial use, sharing, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if you m

FAQs

What makes cytokine-induced killer (CIK) cells distinct for immunotherapy?

CIK cells are an MHC-unrestricted immune effector subgroup with cytotoxic activity against hematologic and solid malignancies, and they are associated with low incidence of severe treatment-related complications.

How are CIK cells composed and which cells are the primary effectors?

CIK cells include CD3+/CD56+ NKT cells, CD3−/CD56+ NK cells, and CD3+/CD56− cytotoxic T cells. The CD3+/CD56+ NKT cells are described as the primary effectors.

Do CIK-cell therapies increase GVHD risk in transplantation?

The review reports a very low graft versus host disease (GVHD) risk, including in MHC-mismatched and haploidentical transplantation settings, despite the high T-cell content and low alloreactivity.

Sep 21, 2026

Uploaded by Ezra