2. Academic Validation
  3. Anti-SIA-cIgG enhances chemotherapy effectiveness through PTPN13-regulated tumor stemness in head and neck squamous cell carcinoma

Anti-SIA-cIgG enhances chemotherapy effectiveness through PTPN13-regulated tumor stemness in head and neck squamous cell carcinoma

  • J Transl Int Med. 2026 Mar 26;14(2):237-258. doi: 10.1515/jtim-2026-0040.
Luming Wang 1,  Yangyang Xia 1,  Chenshu Liu 1,  Xiaofeng Shan 1,  Yi Sui 1,  Shang Xie 1,  Zhigang Cai 1
Affiliations

Affiliation

  • 1 Department of Oral and Maxillofacial Surgery, Peking University School and Hospital of Stomatology; National Center for Stomatology; National Clinical Research Center for Oral Diseases; National Engineering Research Center of Oral Biomaterials and Digital Medical Devices; Beijing Key Laboratory of Digital Stomatology; NHC Key Laboratory of Digital Stomatology; NMPA Key Laboratory for Dental Materials, Beijing, China.
PMID: 42046805 DOI: 10.1515/jtim-2026-0040
Abstract

Background and objectives: The chemotherapy response rate in head and neck squamous cell carcinoma (HNSCC) remains low due to a lack of effective therapeutic targets, and treatment efficacy is further limited by chemoresistance and heterogeneity in drug response. Sialylated Cancer IgG (SIA-cIgG) is a tumor-derived immunoglobulin implicated in tumor stemness. However, the relationship between SIA-cIgG and chemoresistance, and its potential as a therapeutic target, remain to be determined.

Methods: We evaluated the antitumor eficacy of SIA-cIgG inhibition combined with four chemotherapeutic agents using two HNSCC cell lines with high or low SIA-cIgG expression, along with in vivo xenograft models. Furthermore, we investigated the functional roles of SIA-cIgG and its downstream effector PTPN13 in regulating HNSCC stemness. Patient-derived organoids (PDOs) from 25 HNSCC patients were used to compare the antitumor eficacy of anti-SIA-cIgG-based combinations against conventional clinical chemotherapy regimens.

Results: Elevated SIA-cIgG protein levels correlated positively with an increased IC50 for cisplatin and poorer chemotherapy response. SIA-cIgG/PTPN13 axis was critical for tumor stemness and chemoresistance. Anti-SIA-cIgG treatment enhanced PTPN13 protein stability and upregulated PTPN13 mRNA expression via SP1. Anti-SIA-cIgG-based drug combinations demonstrated significantly higher Anticancer efficacy than conventional clinical chemotherapy regimens and overcame tumor heterogeneity in drug response.

Conclusions: SIA-cIgG/PTPN13 axis regulates tumor stemness and contributes to chemoresistance, anti-SIA-cIgG-based drug combinations exhibit significant potential for clinical application.

Keywords

PTPN13; SIA-cIgG; chemoresistance; head and neck squamous cell carcinoma; patient-derived organoids; tumor stemness.

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