Is Triple-Negative Breast Cancer Really That Frightening? Should Cell-Based Immunotherapy Be Considered?
What the Latest Science Says About NK and CIK Cells
From the perspective of treating advanced and relapsed diseases, understand the role of NK/CIK cells in “maintenance control” and immune repair.
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Why Does Triple-Negative Breast Cancer Cause So Much Anxiety Among Patients?
Triple-negative breast cancer (TNBC) is defined by the absence of estrogen receptors, progesterone receptors, and HER2 expression, accounting for approximately 15–20% of all breast cancers. Compared with other subtypes, TNBC often affects younger patients, shows poorer pathological differentiation, and is characterized by aggressive behavior, with higher rates of recurrence, metastasis, and mortality.
Because TNBC lacks clear molecular targets, hormone therapy and HER2-targeted therapy are ineffective. Treatment therefore relies mainly on chemotherapy and selected immunotherapies. For many patients—especially those facing recurrence or metastasis—this reality creates a strong need for treatment strategies that can maintain disease control over time, rather than provide only short-term tumor shrinkage.
For patients with adequate physical condition, combination chemotherapy remains a standard option for advanced or metastatic TNBC. However, clinical experience shows that even when tumors initially respond to chemotherapy, disease progression may accelerate rapidly once treatment is discontinued.
As a result, maintenance therapy has become a critical component of TNBC management. The goal of maintenance therapy is not aggressive tumor eradication, but long-term suppression of tumor activity, delayed recurrence, improved quality of life, and prolonged survival—while keeping treatment toxicity manageable.
Advanced TNBC Treatment: Control Alone Is Not Enough—Maintenance Matters
What Is Metronomic Chemotherapy, and Why Is It Suitable for TNBC?
Metronomic chemotherapy refers to the continuous administration of low-dose chemotherapy at short, regular intervals without long drug-free breaks. Unlike conventional high-dose chemotherapy, its mechanisms extend beyond direct tumor cell killing and include:
- Inhibition of tumor angiogenesis
- Modulation of immune responses
- Induction of tumor cell dormancy
Because of its relatively low toxicity and good tolerability, metronomic chemotherapy is well suited as a maintenance strategy for recurrent or metastatic TNBC and provides a favorable foundation for combination with immunotherapy.
Why Is Immune Function Especially Important in TNBC?
Cancer progression is not driven solely by tumor cells; it also reflects the ongoing interaction between tumors and the immune system. While chemotherapy can effectively eliminate cancer cells, it often suppresses immune function at the same time, limiting the body’s ability to sustain anti-tumor defense.
TNBC is highly heterogeneous. Even when most tumor cells are eliminated, a small population of resistant cells may remain, eventually leading to relapse or metastasis. Therefore, restoring and strengthening immune function during treatment is a key factor in prolonging disease control.
What Are NK and CIK Cells, and Why Are They Considered Key Anti-Cancer Allies?
Cytokine-induced killer (CIK) cells are immune effector cells that combine characteristics of both T lymphocytes and natural killer (NK) cells. They possess the tumor-specific cytotoxicity of T cells as well as the non–MHC-restricted killing ability of NK cells, allowing them to attack tumor cells without prior antigen sensitization.
NK and CIK cells can directly kill tumor cells and regulate the immune microenvironment, improving overall immune competence. For this reason, NK/CIK cell therapy is considered one of the more mature and relatively safe forms of adoptive cellular immunotherapy.
Key Clinical Evidence: DC-CIK Combined With Metronomic Chemotherapy
A study published in 2021 in the Journal of BUON analyzed clinical data from 110 patients with recurrent or metastatic TNBC. The study evaluated the efficacy and safety of metronomic capecitabine chemotherapy combined with autologous dendritic cell–CIK (DC-CIK) immunotherapy.
Patients were divided into two groups:
- A DC-CIK plus metronomic chemotherapy group
- A metronomic chemotherapy–only control group
The results demonstrated that patients receiving DC-CIK combination therapy achieved significantly higher objective response rates, improved disease control rates, and longer disease control duration compared with chemotherapy alone.
Immune Recovery and Quality of Life: Outcomes That Matter to Patients
After treatment, patients in the DC-CIK group showed significant increases in CD3+ T cells, CD4+ T cells, and NK cells, along with an improved CD4/CD8 ratio—indicating immune system reactivation.
Equally important, quality-of-life assessments revealed improvement in both groups, but patients receiving DC-CIK therapy experienced greater emotional and psychological well-being. This highlights that immune cell therapy contributes not only to tumor control, but also to meaningful improvements in daily life and emotional health.
Why Cell-Based Immunotherapy Helps Address Residual and Drug-Resistant Tumor Cells
Tumor heterogeneity means that while chemotherapy can eliminate most cancer cells, a small population of drug-resistant cells often survives and drives relapse. Previous studies have shown that CIK cells remain highly effective against multidrug-resistant cancer cells.
By combining metronomic chemotherapy with NK/CIK cell therapy, residual cancer cells that escape chemotherapy can be targeted by immune mechanisms, extending disease control and reducing the risk of recurrence.
How Should Patients View the Role of NK/CIK Cell Therapy?
NK/CIK cell therapy is not intended to replace chemotherapy, but rather to function as an immune-supportive and immune-restorative strategy. For patients with recurrent or metastatic TNBC, this approach offers a potential path that balances efficacy with tolerability.
Under proper medical supervision, combining metronomic chemotherapy with immune cell therapy may allow patients to achieve longer periods of disease stability, improved immune resilience, and better quality of life.
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References
- Chen, J.-Y. (2021). Capecitabine metronomic chemotherapy combined with dendritic cell–cytokine-induced killer cell immunotherapy in recurrent or metastatic triple-negative breast cancer. Journal of BUON, 26(4).
https://www.jbuon.com/article/6711/ - Thacker, G., Henry, S., Nandi, A., et al. (2023). Immature natural killer cells promote progression of triple-negative breast cancer. Science Translational Medicine, 15(686), eabl4414.
https://doi.org/10.1126/scitranslmed.abl4414