Heat Shock Protein 105 as an Immunotherapeutic Target for Patients With Cervical Cancer

Anticancer Res. 2021 Oct;41(10):4741-4751. doi: 10.21873/anticanres.15289.

Abstract

Background/aim: Heat shock protein 105 (HSP105) is overexpressed in various cancers, but not in normal tissues. We investigated the expression levels of HSP105 in cervical cancer and the efficacy of immunotherapy targeting HSP105.

Materials and methods: Previously, we established human leukocyte antigen-A*02:01 (HLA-A2) restricted HSP105 peptide-specific cytotoxic T lymphocyte (CTL) clones from a colorectal cancer patient vaccinated with an HSP105 peptide. Herein, we evaluated the expression of HSP105 in cervical cancer and cervical intraepithelial neoplasia. Moreover, we tested the effectiveness of an HLA-A2-restricted HSP105 peptide-specific CTL clone against cervical cancer cell lines.

Results: HSP105 was expressed in 95% (19/20) of examined cervical cancer tissues. Moreover, the HSP105 peptide-specific CTL clone recognized HSP105- and HLA-A*02:01-positive cervical cancer cell lines and also showed that cytotoxicity against the cervical cancer cell lines depends on HSP105 peptide and HLA class I restricted manners.

Conclusion: HSP105 could be an effective target for immunotherapy in patients with cervical cancer.

Keywords: Heat shock protein 105; cancer germline antigen; cancer immunotherapy; cervical cancer; cytotoxic T lymphocyte clone.

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Female
  • HLA-A2 Antigen / immunology
  • HLA-A2 Antigen / metabolism
  • HSP110 Heat-Shock Proteins / immunology*
  • HSP110 Heat-Shock Proteins / metabolism
  • Humans
  • Immunotherapy / methods*
  • Mice
  • T-Lymphocytes, Cytotoxic / immunology
  • T-Lymphocytes, Cytotoxic / transplantation
  • Uterine Cervical Neoplasms / immunology
  • Uterine Cervical Neoplasms / metabolism
  • Uterine Cervical Neoplasms / therapy*
  • Xenograft Model Antitumor Assays

Substances

  • HLA-A*02:01 antigen
  • HLA-A2 Antigen
  • HSP110 Heat-Shock Proteins
  • HSPH1 protein, human