Related Experiment Video
Updated: Jul 10, 2026
Assessment of Human Natural Killer Cell Events Driven by FcγRIIIa Engagement in the Presence of Therapeutic Antibodies
Published on: May 22, 2020
CD69 on CD56+ NK cells and response to chemoimmunotherapy in metastatic melanoma
G Konjević1, V Jović, A Vuletić
1Institute for Oncology and Radiology of Serbia, Pasterova 14, Belgrade, Serbia and Montenegro. konjevicg@ncrc.ac.yu
Background:
The few chemoimmunotherapy trials that together with dacarbazine (DTIC) and interferon-alpha 2a (IFNalpha), include retinoic acid (RA), did not include detailed immunological evaluation of functional and phenotypic natural killer (NK) cell characteristics, and have shown contradictory clinical results.
Materials And Methods:
Malignant melanoma (MM) patients undergoing phase II-randomized chemoimmunotherapy trials were treated with DTIC, IFNalpha (Hoffmann-La Roche) (group A, n = 31), and with DTIC, IFNalpha and 13-cis-RA (Isotretinoin, Hoffmann-La Roche, Basel, Switzerland) (group B, n = 29). Patients and 42 healthy controls were evaluated by FACS flow analyses for CD3/CD56/CD69 positive cells, NK cytotoxicity in fresh peripheral blood lymphocytes (PBL) and for interferon regulatory factor-1 mRNA expression by reverse transcriptase polymerase chain reaction in treated PBL.
Results:
The addition of RA to a DTIC-IFN regime did not bring any therapeutical benefit in terms of response or survival. Immunological follow-up on days 1, 6 and 27 of each therapy cycle shows a significant increase in NK cell activity in both groups, only on day 6 of the first cycle, while CD69+CD56+ expression increased significantly on day 6 of each therapy cycle, in both groups. Evaluation of the dynamics of expression of IRF-1 of in vitro treated PBL, shows its strong and prompt up-regulation by IFNalpha and synergistic effect of IFNalpha and RA combination.
Conclusion:
The dynamics of the increase in CD69 early activation antigen expression on CD56+ NK cells is systematic and serial with the increase being significantly higher on day six of the first cycle in group B patients with clinical response, compared to those without, indicating possible predictive value of CD69 expression for clinical response to chemoimmunotherapy.
Insights
Adding retinoic acid to dacarbazine and interferon-alpha did not improve melanoma treatment outcomes. However, increased CD69 expression on natural killer cells may predict clinical response to chemoimmunotherapy.
Area of Science:
- Immunology
- Oncology
- Pharmacology
Background:
- Chemoimmunotherapy trials combining dacarbazine (DTIC), interferon-alpha 2a (IFNalpha), and retinoic acid (RA) for malignant melanoma (MM) have yielded inconsistent clinical results.
- These trials often lacked detailed immunological evaluations of natural killer (NK) cell function and phenotype.
Purpose of the Study:
- To evaluate the impact of adding 13-cis-retinoic acid (RA) to a DTIC-IFNalpha regimen on MM treatment outcomes.
- To conduct a detailed immunological assessment of NK cell characteristics and interferon regulatory factor-1 (IRF-1) expression in patients undergoing chemoimmunotherapy.
Main Methods:
- A phase II randomized trial compared DTIC + IFNalpha (group A, n=31) with DTIC + IFNalpha + RA (group B, n=29) in MM patients.
- Flow cytometry (FACS) analyzed CD3/CD56/CD69 expression on peripheral blood lymphocytes (PBL).
- NK cell cytotoxicity assays and reverse transcriptase polymerase chain reaction for IRF-1 mRNA were performed on PBL.
Main Results:
- The addition of RA to the DTIC-IFNalpha regimen did not improve therapeutic response or survival rates.
- Both groups showed a significant increase in NK cell activity on day 6 of the first cycle.
- CD69 expression on CD56+ NK cells increased significantly on day 6 of each cycle in both groups.
- In vitro studies demonstrated prompt IRF-1 upregulation by IFNalpha, with a synergistic effect when combined with RA.
Conclusions:
- The addition of RA to DTIC-IFNalpha does not offer clinical benefit for MM patients.
- The dynamics of CD69 expression on NK cells show a potential predictive value for clinical response to chemoimmunotherapy.
- Specifically, higher CD69 expression on day six of the first cycle in group B patients correlated with clinical response.
Related Concept Videos
01:27Cytotoxic T Cells-mediated Immune Response
Immunological surveillance is the ability of immune cells to monitor and eliminate infected cells with intracellular pathogens, neoplastically transformed cells, and cells with non-self antigens. Cytotoxic T cells and NK...
01:27Tumor Immunotherapy