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This research investigates the combined effect of cisplatin and oral microbiota on HNSCC aggression and the underlying mechanisms.

April 5, 2026

Abstract 4810: Cisplatin-oral microbiota synergistic role in HNSCC aggressiveness and its clinical relevance

Key Points

This research investigates the combined effect of cisplatin and oral microbiota on HNSCC aggression and the underlying mechanisms.
Collected saliva samples from 15 HNSCC patients before cisplatin treatment.
Analyzed microbiome composition using 16S rRNA gene sequencing and qPCR targeting specific bacteria.
Conducted in vitro experiments by co-culturing HNSCC cells with oral bacteria and treating with cisplatin.
Assessed recovery through colony formation, migration, and stemness marker expression.
Correlated post-therapy salivary microbiota with patient outcomes and tumor profiles.
Co-exposure to cisplatin and oral bacteria induced a TSD-like phenotype in HNSCC cells.
Elevated expression of stemness markers (HIF-2α, ABCG2, Myc) was observed in treated cells.
Higher clonogenic survival and migration capacity in joint treatment group.
Increased microbial LPS load and F. nucleatum presence correlated with poor chemotherapy response.
Identified potential for targeting microbiota interactions to reduce treatment relapse.

Abstract

Abstract Background: Cisplatin-based chemotherapy remains a cornerstone for treating Head and NeckSquamous Cell Carcinoma (HNSCC). However, its therapeutic success is often limited inpatients with advanced-stage disease (Stage III-IIIb). Emerging evidence indicates thatchemotherapy itself may induce or select for aggressive, therapy-resistant tumor phenotypes.Meanwhile, dysbiosis of the oral microbiota—particularly involving Fusobacterium nucleatumand Porphyromonas gingivalis—has been implicated in HNSCC progression and immuneevasion. Yet, the synergistic interplay between cisplatin treatment and oral microbial ecologyremains poorly understood. Here, we investigate whether oral microbiota enhance cisplatin-induced aggressiveness via reprogramming of cancer stem cell (CSC) phenotypes, particularlythe Tumor Stemness Defense (TSD) state, which represents an adaptive altruistic response totherapy-induced stress. Methods: Saliva samples were prospectively collected from 15 HNSCC patients prior toinitiation of cisplatin-based chemotherapy. The microbiome composition was analyzed using16S rRNA gene sequencing and targeted qPCR for F. nucleatum and P. gingivalis. In vitro,these isolates were co-cultured with SAS HNSCC cells (MOI 50:1) and treated with cisplatin(1-5 µM) for three days. Post-treatment recovery was monitored up to 14 days, withassessments of colony formation, migration, and expression of TSD-associated stemnessmarkers (EpCAM, ABCG2, HIF-2α, Myc, SOX2, OCT4, NANOG). Clinically, post-therapysalivary microbiota was correlated with patient outcomes and tumor hypoxia profiles. Results: Co-exposure of SAS cells to cisplatin and F. nucleatum or P. gingivalis led to theemergence of a TSD-like phenotype, characterized by elevated expression of HIF-2α, ABCG2,and Myc, increased clonogenic survival, and enhanced migration capacity. Thisreprogramming effect was attenuated by TLR4 inhibition. Patient saliva analysis revealed thatelevated microbial LPS load and enrichment of F. nucleatum correlated with poorchemotherapy response and higher CTC count during treatment. Conclusion: Our findings reveal that the oral microbiota synergizes with cisplatin to promotetherapy-induced adaptive stemness in HNSCC. This mechanism, involving microbialLPS/TLR4 signaling and HIF-2α activation, suggests that oral microbial dysbiosis may act asa co-driver of tumor evolution under chemotherapeutic stress. Targeting microbiota-chemotherapy interactions may offer a new avenue to reduce post-therapy relapse. References: 1. doi: 10.3389/fimmu.2024.1336882 2. doi: 10.3389/fimmu.2023.1198269 3. doi:10.1620/tjem.253.249. PMID: 33840648. Citation Format: Partha Jyoti Saikia, Lekhika Pathak, Bidisha Pal, Upasha Sarmah, Tulika Sarma, Chayanika Das, Debduti Datta, Rupam Das, Bikul Das. Cisplatin-oral microbiota synergistic role in HNSCC aggressiveness and its clinical relevance abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 4810.

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