The Ability of Clinically Relevant Chemotherapeutics to Induce Immunogenic Cell Death in Squamous Cell Carcinoma

Front Biosci (Landmark Ed). 2024 Apr 22;29(4):158. doi: 10.31083/j.fbl2904158.


Background: Immunogenic cell death (ICD) is a crucial mechanism for triggering the adaptive immune response in cancer patients. Damage-associated molecular patterns (DAMPs) are critical factors in the detection of ICD. Chemotherapeutic drugs can cause ICD and the release of DAMPs. The aim of this study was to assess the potential for paclitaxel and platinum-based chemotherapy regimens to induce ICD in squamous cell carcinoma (SCC) cell lines. In addition, we examined the immunostimulatory effects of clinically relevant chemotherapeutic regimens utilized in the treatment of SCC.

Methods: We screened for differentially expressed ICD markers in the supernatants of three SCC cell lines following treatment with various chemotherapeutic agents. The ICD markers included Adenosine Triphosphate (ATP), Calreticulin (CRT), Annexin A1 (ANXA 1), High Mobility Group Protein B1 (HMGB1), and Heat Shock Protein 70 (HSP70). A vaccination assay was also employed in C57BL/6J mice to validate our in vitro findings. Lastly, the levels of CRT and HMGB1 were evaluated in Serum samples from SCC patients.

Results: Addition of the chemotherapy drugs cisplatin (DDP), carboplatin (CBP), nedaplatin (NDP), oxaliplatin (OXA) and docetaxel (DOC) increased the release of ICD markers in two of the SCC cell lines. Furthermore, mice that received vaccinations with cervical cancer cells treated with DDP, CBP, NDP, OXA, or DOC remained tumor-free. Although CBP induced the release of ICD-associated molecules in vitro, it did not prevent tumor growth at the vaccination site in 40% of mice. In addition, both in vitro and in vivo results showed that paclitaxel (TAX) and LBP did not induce ICD in SCC cells.

Conclusion: The present findings suggest that chemotherapeutic agents can induce an adjuvant effect leading to the extracellular release of DAMPs. Of the agents tested here, DDP, CBP, NDP, OXA and DOC had the ability to act as inducers of ICD.

Keywords: chemotherapy; damage-associated molecular pattern; immunogenic cell death; squamous carcinoma.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adenosine Triphosphate / metabolism
  • Animals
  • Annexin A1 / metabolism
  • Antineoplastic Agents* / pharmacology
  • Antineoplastic Agents* / therapeutic use
  • Calreticulin* / metabolism
  • Carboplatin / pharmacology
  • Carcinoma, Squamous Cell* / drug therapy
  • Carcinoma, Squamous Cell* / immunology
  • Carcinoma, Squamous Cell* / pathology
  • Cell Line, Tumor
  • Cisplatin* / pharmacology
  • Docetaxel / pharmacology
  • Docetaxel / therapeutic use
  • Female
  • HMGB1 Protein* / metabolism
  • HSP70 Heat-Shock Proteins / metabolism
  • Humans
  • Immunogenic Cell Death* / drug effects
  • Mice
  • Mice, Inbred C57BL*
  • Organoplatinum Compounds* / pharmacology
  • Oxaliplatin / pharmacology
  • Paclitaxel* / pharmacology
  • Paclitaxel* / therapeutic use


  • HMGB1 Protein
  • Calreticulin
  • Cisplatin
  • Antineoplastic Agents
  • Paclitaxel
  • Organoplatinum Compounds
  • Oxaliplatin
  • Carboplatin
  • Docetaxel
  • nedaplatin
  • Adenosine Triphosphate
  • HSP70 Heat-Shock Proteins
  • Annexin A1