By: [Dr. Ari Herlina]
Introduction: The Urgency of New Modalities Breast cancer remains the greatest global oncology challenge. GLOBOCAN 2024 data recorded more than 2 million new cases, making it the malignancy with the highest incidence in women, including in Indonesia. Although surgery, chemotherapy, and hormonal therapy are the standard of care, clinical challenges such as drug resistance, relapse, and severe toxicity still hinder the achievement of long-term remission. This situation has prompted a paradigm shift towards cellular immunotherapy, particularly the use of Cytokine-Induced Killer (CIK) cells.
CIK Cell Profile: “Hybrid Soldiers” of the Immune System CIK cells are a heterogeneous population of lymphocytes that are expanded ex vivo and have unique characteristics. CIK cells have dual cytotoxic activity; they express T cell (CD3+) and Natural Killer (CD56+) cell markers. The main advantage of CIK is their ability to kill tumor cells in a non-MHC-restricted manner. Through the NKG2D receptor, CIK cells recognize stress ligands on the surface of cancer cells, allowing them to destroy tumor cells that often hide MHC molecules to avoid immune detection.
Clinical Synergy: Why Are Combination Regimens Superior? Current evidence shows that CIK works most effectively in combination strategies:
1. Combination with Chemotherapy (Chemo-Immunotherapy) Cytotoxic drugs such as Doxorubicin or Taxane not only kill cancer cells directly, but also modulate tumor immunogenicity. Chemotherapy can increase the expression of NKG2D ligands on tumor cells, making cancer more “visible” and vulnerable to CIK cell attacks.
2. Combination with Targeted Therapy (HER2) In HER2-positive breast cancer subtypes, the combination of CIK with Trastuzumab shows synergistic effects. Monoclonal antibodies block cancer cell growth signals, while CIK cells provide additional cytotoxic effects, potentially overcoming resistance to single-target therapy.
3. Combination with Checkpoint Inhibitors (ICIs) The addition of immune checkpoint inhibitors (such as anti-PD-1/PD-L1) prevents immune cell “exhaustion.” ICIs release the brakes on the immune system, allowing CIK cells to work more aggressively and persistently in the tumor microenvironment.
Clinical Evidence and Safety A recent phase I/II study (Jiang et al., 2025) reported that the CIK combination regimen delivered promising clinical results:
• Efficacy: Improved Objective Response Rate (ORR) and prolonged Progression-Free Survival (PFS) compared to standard therapy alone.
• Safety: The toxicity profile is well tolerated. Side effects are generally mild and temporary (such as mild fever or fatigue), without an increased risk of severe infections or significant autoimmune phenomena.
Challenges and Future Despite its promise, widespread adoption of CIK therapy faces challenges related to high production costs and the need for standardized cell culture protocols. The future of this therapy lies in a personalized approach, where combination regimens are tailored to the patient’s tumor molecular profile for optimal outcomes.
Conclusion Cytokine-Induced Killer (CIK) cells represent a significant advancement in breast cancer immunotherapy. When combined with chemotherapy or targeted therapy, CIK offers an effective and safe “dual attack” strategy, opening new hope for patients with refractory or advanced-stage cases.
References Jiang Y, Qiu J, Ye N, Xu Y. (2025). Current status of cytokine-induced killer cells and combination regimens in breast cancer. Frontiers in Immunology; 16:147664. doi: 10.3389/fimmu.2025.1476644.
