Neoadjuvant cisplatin and paclitaxel modulate tumor-infiltrating T cells in patients with cervical cancer.

Abstract

Resistance to chemotherapy is widely recognized as one of the major factors limiting therapeutic efficacy and influences clinical outcomes in patients with cancer. Many studies on various tumor types have focused on combining standard-of-care chemotherapy with immunotherapy. However, for cervical cancer, the role of neoadjuvant chemotherapy (NACT) on the local immune microenvironment is largely unexplored. We performed a pilot study on 13 primary cervical tumor samples, before and after NACT, to phenotype and enumerate tumor-infiltrating T-cell subpopulations using multiplex immunohistochemistry (CD3, CD8, FoxP3, Ki67, and Tbet) and automated co-expression analysis software. A significant decrease in proliferating (Ki67+) CD3+CD8- T cells and FoxP3+(CD3+CD8-) regulatory T cells was observed in the tumor stroma after cisplatin and paclitaxel treatment, with increased rates of cytotoxic CD8+ T cells, including activated and CD8+Tbet+ T cells. No effect was observed on the number of tumor-infiltrating T cells in the cervical tumor microenvironment after treatment with cisplatin only. Therefore, we conclude that patients treated with cisplatin and paclitaxel had more tumor-infiltrating T-cell modulation than patients treated with cisplatin monotherapy. These findings enhance our understanding of the immune-modulating effect of chemotherapy and warrant future combination of the standard-of-care therapy with immunotherapy to improve clinical outcome in patients with cervical cancer.

• Authors: A Marijne Heeren, Iske F van Luijk, Joost Lakeman, Noëlle Pocorni, Jeroen Kole, Renée X de Menezes, Gemma G Kenter, Tjalling Bosse, Cornelis D de Kroon, Ekaterina S Jordanova
• Journal: Cancer immunology, immunotherapy : CII (Cancer Immunol Immunother) Vol. 68 Issue 11 Pg. 1759-1767 (Nov 2019) ISSN: 1432-0851 [Electronic] Germany
• PMID: 31616965 (Publication Type: Journal Article)

Chemical References

• Paclitaxel
• Cisplatin

Topics

• Adult
• Antineoplastic Combined Chemotherapy Protocols (therapeutic use)
• Chemotherapy, Adjuvant
• Cisplatin (administration & dosage)
• Female
• Follow-Up Studies
• Humans
• Lymphocytes, Tumor-Infiltrating (immunology)
• Male
• Middle Aged
• Neoadjuvant Therapy (methods)
• Paclitaxel (administration & dosage)
• Pilot Projects
• Prognosis
• Retrospective Studies
• T-Lymphocytes, Regulatory (immunology)
• Uterine Cervical Neoplasms (drug therapy, immunology, pathology)
• Young Adult