Abstract
Abstract 63: Intratumoral Candida albicans associates with hypoxia and poor outcomes in non small cell lung cancer (NSCLC)
Cancer research (Chicago, Ill.), Vol.86(7_Supplement), pp.63-63
04/03/2026
DOI: 10.1158/1538-7445.AM2026-63
Abstract
Resistance to radiation, chemotherapy, and immunotherapy remains a major challenge in non-small cell lung cancer (NSCLC), and emerging evidence suggests tumor-resident microbes may influence therapeutic response. To address this, we combined patient-level modeling with mechanistic studies in preclinical models. We first analyzed RNA-sequencing data from 2,156 NSCLC tumors collected under the Total Cancer Care Protocol (NCT03977402) within the ORIEN network using a contamination-aware pipeline to quantify intratumoral Candida albicans (CA) and assess its impact on treatment outcomes. We developed MEC-TX (Mechanistic Clustering Treatment), a digital-twin framework that compares patients receiving similar treatment regimens differing only by CA burden. CA was detected in ∼55% of tumors; high CA burden was associated with significantly shorter overall survival (hazard ratio 1.6, p < 0.01), and similar trends were observed in radiation- and chemotherapy-treated cohorts defined by MEC-TX. After adjusting for clinical covariates (age, sex, stage, BMI), CA remained an independent predictor of poor survival, underscoring MEC-TX’s ability to isolate biologically meaningful signals. Transcriptomic profiling revealed CA-high tumors had elevated hypoxia-related gene expression (p = 0.0045), suggesting a link between fungal infiltration and tumor microenvironment. To test this, we implanted Lewis lung carcinoma cells into syngeneic C57BL/6 mice and gavaged them with CA, Blautia obeum (commensal control), or saline (vehicle control). CA-gavaged tumors were significantly larger (p = 0.0108) and exhibited lower pH (p = 0.024) and reduced intratumoral pO2 (p = 0.051) compared to controls, as measured by EPR oximetry, after adjusting for tumor size, supporting CA’s role in creating a hypoxic, therapy-resistant niche. In vitro, CA-conditioned media conferred radioresistance across multiple cell lines (p = 0.001), implicating secreted molecules as drivers of this phenotype. Collectively, these findings reveal a novel mechanism by which intratumoral fungi promote hypoxia and treatment resistance, providing a strong rationale for microbiome-informed strategies to overcome hypoxia-driven resistance and improve precision oncology.
Details
- Title: Subtitle
- Abstract 63: Intratumoral Candida albicans associates with hypoxia and poor outcomes in non small cell lung cancer (NSCLC)
- Creators
- Dipankor Chatterjee - The Ohio State UniversityDennis J. Grencewicz - The Ohio State UniversityAlexander Loncar - The Ohio State UniversityRuohan Wu - The Ohio State University Wexner Medical CenterAlex Samouilov - The Ohio State UniversitySylvain Ferrandon - The Ohio State UniversityMcKenzie Kreamer - The Ohio State UniversityYogita Mehra - The Ohio State UniversityAspen Carson - The Ohio State UniversityRebecca Hoyd - The Ohio State UniversityShiva Jahanbakhshi - The Ohio State UniversityFouad Choueiry - The Ohio State UniversityMatthew AndersonMartin Benej - The Ohio State UniversityDustin Bosch - University of IowaJiangjiang (Chris) Zhu - The Ohio State UniversityJinghai Wu - The Ohio State UniversityThèrése Bocklage - Markey Cancer CenterMartin McCarter - University of Colorado Anschutz Medical CampusAhmad Tarhini - Moffitt Cancer CenterBodour Salhia - USC Norris Comprehensive Cancer CenterChristopher A. Moskaluk - University of Virginia Health SystemGregory Riedlinger - Rutgers, The State University of New JerseySong Yao - Roswell Park Comprehensive Cancer CenterAshiq Masood - Indiana University HealthSheetal Hardikar - Huntsman Cancer InstituteMmadili N. Ilozumba - Huntsman Cancer InstituteCornelia M. Ulrich - Huntsman Cancer InstituteAbdul Rafeh Naqash - University of Oklahoma Health Sciences CenterCarlos H.F. Chan - University of IowaCraig D. Shriver - Uniformed Services University of the Health SciencesDinesh Pal Mudaranthakam - University of Kansas Medical CenterAaditya Pallerla - University of CincinnatiMichelle Churchman - Hudson InstituteRobert J. Rounbehler - Clinical InsightsLaura Chambers - The Ohio State UniversityMatthew F. Kalady - The Ohio State UniversityNicholas C. Denko - The Ohio State UniversityDavid P. Carbone - The Ohio State UniversityDan Spakowicz - The Ohio State University
- Resource Type
- Abstract
- Publication Details
- Cancer research (Chicago, Ill.), Vol.86(7_Supplement), pp.63-63
- DOI
- 10.1158/1538-7445.AM2026-63
- ISSN
- 0008-5472
- eISSN
- 1538-7445
- Publisher
- AMER ASSOC CANCER RESEARCH
- Language
- English
- Date published
- 04/03/2026
- Academic Unit
- Pathology
- Record Identifier
- 9985152089702771
Metrics
1 Record Views