J Korean Med Sci.  2019 Nov;34(44):e272. 10.3346/jkms.2019.34.e272.

Role of Immunosuppressive Microenvironment in Acquiring Immunotolerance Post-Photothermal Therapy

• Cherukula
• Park MS
• Sontyana A
• Mathew AP
• Vijayan V
• Bae WK
• Park IK

• KMID: 2462185
• DOI: http://doi.org/10.3346/jkms.2019.34.e272

Abstract

BACKGROUND
Nanoparticle-mediated photothermal therapy (PTT) has been well studied as a treatment for cancer. However, the therapeutic outcome of PTT is often hindered by the penetration depth of laser light. In the tumor margin beyond the laser penetration limit, tumor recurrence often occurs, bypassing the immune response of the host. Accumulating evidence suggests the prominent role of tumor microenvironment (TME) and its interactions with the immune components contribute to an immunosuppressive milieu during the post-therapy period. Here, we explored the immunosuppressive cascade generated after PTT, which is responsible for tumor recurrence, and identified the potential targets to achieve an effective PTT period.
METHODS
Here, we investigated the immunosuppressive cascade generated after PTT in a CT26 tumor bearing mouse. The liposomal system loaded with the indocyanine green (ICG) was utilized for the generation of PTT with high efficiency. Immunological factors such as cytokines and protein expressions post-therapy were investigated through enzyme-linked immunosorbent assay, flow cytometry and western blot analysis.
RESULTS
Our results suggested that PTT with ICG-loaded liposomes (Lipo-ICG) was effective for the first 5 days after treatment, resulting in tumor suppression. However, an immunosuppressive and pro-inflammatory environment developed thereafter, causing the recruitment and upregulation of the immune evasion factors of heat shock protein 70, programmed death ligand 1, indoleamine-dioxygenase, interleukin-6, transforming growth factor-β, regulatory T-cells, and myeloid-derived suppressor cells, to develop immunotolerance.
CONCLUSION
Collectively, these findings have determined potential therapeutic targets to modulate the TME during PTT and achieve tumor ablation without remission.

Keyword

Photothermal Therapy; Immunosuppression; Tumor Microenvironment; Immunosuppression

MeSH Terms

Animals
Blotting, Western
Cytokines
Enzyme-Linked Immunosorbent Assay
Flow Cytometry
HSP70 Heat-Shock Proteins
Immune Evasion
Immunologic Factors
Immunosuppression
Indocyanine Green
Interleukin-6
Liposomes
Mice
Recurrence
T-Lymphocytes, Regulatory
Tumor Microenvironment
Up-Regulation
Cytokines
HSP70 Heat-Shock Proteins
Immunologic Factors
Indocyanine Green
Interleukin-6
Liposomes