T-Cell Receptor Repertoires of Tumor-Infiltrating Lymphocytes After Hyperthermia Using Functionalized Magnetite Nanoparticles

Abstract

Aim: Accumulating evidence has indicated that hyperthermia using magnetite nanoparticles induces antitumor immunity. This study investigated the diversity of T-cell receptors (TCRs) in tumor-infiltrating lymphocytes after hyperthermia using magnetite nanoparticles.Materials & methods: Functionalized magnetite nanoparticles, N-propionyl-4-S-cysteaminylphenol (NPrCAP)/magnetite, were synthesized by conjugating the melanogenesis substrate NPrCAP with magnetite nanoparticles. NPrCAP/magnetite nanoparticles were injected into B16 melanomas in C57BL/6 mice, which were subjected to an alternating magnetic field for hyperthermia treatment. Results: Enlargement of the tumor-draining lymph nodes was observed after hyperthermia. The TCR repertoire was restricted in tumor-infiltrating lymphocytes, and expansion of Vβ11⁺ T cells was preferentially found. DNA sequences of the third complementaritydetermining regions revealed the presence of clonally expanded T cells. Conclusion: These results indicate that the T-cell response in B16 melanomas after hyperthermia is dominated by T cells directed toward a limited number of epitopes and that epitope-specific T cells frequently use a restricted TCR repertoire.

Original submitted 14 May 2012; Revised submitted 30 July 2012; Published online 15 October 2012

KEYWORS::

• hyperthermia
• magnetite nanoparticle
• melanoma
• T-cell receptor
• tumor-infiltrating lymphocyte

Financial & competing interests disclosure

This work was supported by Health and Labour Sciences Research Grants-in-Aid (H21-nano-006) for Research on Advanced Medical Technology from the Ministry of Health, Labour and Welfare of Japan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

No writing assistance was utilized in the production of this manuscript.

Ethical conduct of research

The authors state that they have obtained appropriate institutional review board approval or have followed the principles outlined in the Declaration of Helsinki for all human or animal experimental investigations. In addition, for investigations involving human subjects, informed consent has been obtained from the participants involved.

Additional information

Funding

This work was supported by Health and Labour Sciences Research Grants-in-Aid (H21-nano-006) for Research on Advanced Medical Technology from the Ministry of Health, Labour and Welfare of Japan. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.