Exploring novel immunotherapy biomarker candidates induced by cancer deformation

PLoS One. 2024 May 14;19(5):e0303433. doi: 10.1371/journal.pone.0303433. eCollection 2024.

Abstract

Triple-negative breast cancer (TNBC) demands urgent attention for the development of effective treatment strategies due to its aggressiveness and limited therapeutic options [1]. This research is primarily focused on identifying new biomarkers vital for immunotherapy, with the aim of developing tailored treatments specifically for TNBC, such as those targeting the PD-1/PD-L1 pathway. To achieve this, the study places a strong emphasis on investigating Ig genes, a characteristic of immune checkpoint inhibitors, particularly genes expressing Ig-like domains with altered expression levels induced by "cancer deformation," a condition associated with cancer malignancy. Human cells can express approximately 800 Ig family genes, yet only a few Ig genes, including PD-1 and PD-L1, have been developed into immunotherapy drugs thus far. Therefore, we investigated the Ig genes that were either upregulated or downregulated by the artificial metastatic environment in TNBC cell line. As a result, we confirmed the upregulation of approximately 13 Ig genes and validated them using qPCR. In summary, our study proposes an approach for identifying new biomarkers applicable to future immunotherapies aimed at addressing challenging cases of TNBC where conventional treatments fall short.

MeSH terms

  • B7-H1 Antigen / genetics
  • B7-H1 Antigen / metabolism
  • Biomarkers, Tumor* / genetics
  • Biomarkers, Tumor* / metabolism
  • Cell Line, Tumor
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Immunotherapy* / methods
  • Programmed Cell Death 1 Receptor / antagonists & inhibitors
  • Programmed Cell Death 1 Receptor / metabolism
  • Triple Negative Breast Neoplasms* / genetics
  • Triple Negative Breast Neoplasms* / immunology
  • Triple Negative Breast Neoplasms* / therapy

Grants and funding

In our Financial Disclosure, we state that this research received partial support from The Elsa U Pardee Foundation (to J.H.L) and the MCC Patient Gift Fund (to J.H.L). The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.