Biology subjects

Karpinets, T.

Publications and source records attributed to Karpinets, T..

5 recordsLinked to original sources

bioRxiv2026

Distinct Spatial Immune Architectures in Tumor and Tumor-Adjacent Tissues of Early-Stage Non-Small Cell Lung Cancer

Background: Lung cancer remains the leading cause of cancer-related deaths in the United States with over 124,000 estimated deaths for 2026. Previous studies have found that tumor-adjacent lung tissues may provide additional insight into the immune microenvironment of early-stage NSCLC. Methods: Multiplex immunofluorescence (mIF) imaging was performed on 192 tissues from 101 early-stage non-small cell lung cancer patients including 91 matched tumor-adjacent pairs, using three mIF panels. Spatial analyses were performed to identify distinctions between tissues and identify associations with clinical and genomic features. Results: Tumor tissue showed significantly higher densities of T cells, macrophages, B cells, and memory/regulatory populations than adjacent tissue (p<0.001). Tumors exhibited greater spatial heterogeneity, with higher prevalence of spatial patterning (47.7% vs. 31.2%) and more consistently localized organization, whereas adjacent tissue showed stronger individual-cell clustering. Pairwise colocalization (Ripley's L-cross) revealed selective spatial segregation in tumors (including B-cells from memory/regulatory cells and among cytotoxic T-cell subsets) and reduced immune proximity to malignant cells relative to the strong immune-epithelial association in adjacent tissue. Spatial features were linked to genomic features or patient outcomes: tumor neoantigen burden exhibited a positive association with CD3+ T cells in the tumor, while colocalization between CD45RO+CD57+GZMB+ cells and CD57+GZMB+ cells was negatively associated with overall survival outside the tumor. Conclusion: Tumor and adjacent tissues harbor distinct spatial immune architectures, with spatial features displaying associations with genomic features or patient outcomes. These findings highlight immune microenvironment reorganization and the importance of incorporating spatial context from both compartments into risk assessment in NSCLC.

immunology↗

bioRxiv2024

Intratumoral Microbiome of Adenoid Cystic Carcinomas and Comparison with other Head and Neck Cancers

BackgroundAdenoid cystic carcinoma (ACC) is a rare, slow growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. MethodsWe investigated the intratumoral microbiome of 50 ACC tumors and 33 adjacent normal tissues using 16S rRNA gene sequencing. This allowed us to characterize the bacterial communities within ACC and explore potential associations between the bacterial community structure, patients clinical characteristics, and tumor molecular features obtained through RNA sequencing. ResultsBacterial composition in ACC displayed significant differences compared to adjacent normal salivary tissue and exhibited diverse levels of species richness. We identified two main microbial subtypes within ACC: oral-like and gut-like. Oral-like microbiomes, characterized by higher diversity and abundance of genera like Neisseria, Leptotrichia, Actinomyces, Streptococcus, Rothia, and Veillonella (commonly found in healthy oral cavities), were associated with the less aggressive ACC-II molecular subtype and improved patient outcomes. Notably, we identified the same oral genera in oral cancer and in head and neck squamous cell carcinomas. In both cancers, they were part of shared oral communities associated with more diverse microbiome, less aggressive tumor phenotype, and better survival. Conversely, gut-like microbiomes in ACC, featuring low diversity and colonization by gut mucus layer-degrading species like Bacteroides, Akkermansia, Blautia, Bifidobacterium, and Enterococcus, were associated with poorer outcomes. Elevated levels of Bacteroides thetaiotaomicron were independently associated with significantly worse survival, regardless of other clinical and molecular factors. Furthermore, this association positively correlated with tumor cell biosynthesis of glycan-based cell membrane components. ConclusionsOur study uncovers specific intratumoral oral genera as potential pan-cancer biomarkers for favorable microbiomes in ACC and other head and neck cancers. These findings highlight the pivotal role of the intratumoral microbiome in influencing ACC prognosis and disease biology.

microbiology↗

bioRxiv2020

Diversity and composition of gut microbiome of cervical cancer patients by 16S rRNA and whole-metagenome sequencing

PurposeNext generation sequencing has progressed rapidly, characterizing microbial communities beyond culture-based or biochemical techniques. 16S ribosomal RNA gene sequencing (16S) produces reliable taxonomic classifications and relative abundances, while shotgun metagenome sequencing (WMS) allows higher taxonomic and functional resolution at greater cost. The purpose of this study was to determine if 16S and WMS provide congruent information for our patient population from paired fecal microbiome samples. MethodsPatients with locally advanced cervical cancers were enrolled on a prospective, observational clinical trial with a rectal swab sample collected prior to chemoradiation. Bacterial DNA was extracted from each sample and divided in two parts for 16S or WMS sequencing. We used measures of diversity richness and evenness as comparators of 16S and WMS sequencing. Relative abundances of the most common taxa were also compared between both datasets. Both techniques were tested against baseline patient demographics to assess associations identified with either or both methods. ResultsComparative indices were highly congruent between 16S and WMS. The most abundant genera for 16S and WMS data did not overlap. Overlap was observed at the Phylum level, as expected. However, relative abundances correlated poorly between the two methodologies (all p>0.05). Hierarchical clustering of both sequencing analyses identified overlapping enterotypes. Both approaches were in agreement with regard to demographic variables. ConclusionDiversity, evenness and richness are comparable when using 16S and WMS techniques, however relative abundances of individual genera are not. Clinical associations with diversity and evenness metrics were similarly identified with WMS or 16S. ImportanceThe gut microbiome plays an important role in regulating human health and disease. 16S rRNA gene sequencing (16S) and the whole-metagenome shotgun DNA sequencing (WMS) are two approaches to describe the microbial community. 16S sequencing via any amplicon sequencing-based method offers advantages over WMS in terms of precision (specific gene targeting). Additionally, 16S has historically been less costly due to the simplicity of library preparation and it does not require the same level read coverage as WMS. In this study, we performed both sequencing methods on a single rectal swab sample obtained from each cervical cancer patient prior to treatment. We showed that these two methods provide comparable information for diversity, evenness, and richness at higher taxonomic resolution, but are discrepant at a lower resolution. These methodological findings provide valuable information for the design and interpretation of future investigations of the role of the gut microbiome in cancer. Tweet(optional: 256 words, please submit a Tweet that conveys the essential message of your manuscript.) 16S may be sufficient for most initial studies of the gut microbiome in cancer patients, but WMS may be required for analysis of lower level taxonomy. Research supportThis research was supported in part by the Radiological Society of North America Resident/Fellow Award (to L.E.C.), the National Institutes of Health (NIH) through MD Andersons Cancer Center Support Grant P30CA016672, the Emerson Collective and the National Institutes of Health T32 grant #5T32 CA101642-14 (T.T.S). This study was partially funded by The University of Texas MD Anderson Cancer Center HPV-related Cancers Moonshot (L.E.C and A.K.).

microbiology↗

bioRxiv2020

Adaptive changes in the gut microbiome during standard-of-care chemoradiotherapy for gynecologic cancers

BackgroundA diverse and abundant gut microbiome can improve cancer patients treatment response; however, the effect of pelvic chemoradiotherapy (CRT) on gut diversity and composition is unclear. The purpose of this prospective study was to identify changes in the diversity and composition of the gut microbiome during and after pelvic CRT. Materials and MethodsRectal swabs from 58 women with cervical, vaginal, or vulvar cancer from two institutions were prospectively analyzed before CRT (baseline), during CRT (weeks 1, 3, and 5), and at first follow-up (week 12) using 16Sv4 rRNA gene sequencing of the V4 hypervariable region of the bacterial 16S rRNA marker gene. Observed operational taxonomic units (OTUs; representative of richness) and Shannon, Simpson, Inverse Simpson, and Fisher diversity indices were used to characterize alpha (within-sample) diversity. Changes over time were assessed using a paired t-test, repeated measures ANOVA, and linear mixed modeling. Compositional changes in specific bacteria over time were evaluated using linear discriminant analysis effect size. ResultsGut microbiome richness and diversity levels continually decreased throughout CRT (mean Shannon diversity index, 2.52 vs. 2.91; all P <0.01), but were at or near baseline levels in 60% of patients by week 12. Patients with higher gut diversity at baseline had the steepest decline in gut microbiome diversity. Gut microbiome composition was significantly altered during CRT, with increases in Proteobacteria and decreases in Clostridiales, but adapted after CRT, with increases in Bacteroides species. ConclusionAfter CRT, the gut microbiomes diversity tends to return to baseline levels, but its structure and composition remain significantly altered. These changes should be considered when designing studies to analyze the gut microbiome as a predictive or prognostic biomarker in patients who receive pelvic CRT for gynecologic cancers.

cancer biology↗

bioRxiv2019

Dynamic evolution of cervical cancer mutations during chemoradiation using novel sampling approach

ObjectiveThe aim of this study was to validate a whole exome sequencing approach to longitudinally characterize the tumor mutational profile of cervical cancer patients undergoing chemoradiation (CRT). Experimental DesignCervical cancer tumor specimens from twenty-seven patients undergoing chemoradiation were collected before and throughout CRT and whole exome sequencing (WES) was performed to characterize individual mutations and alterations in unique genes. WES data were analyzed from cervical cancer patients in The Cancer Genome Atlas (TCGA) as a comparison group. ResultsOver 93% of mutated genes detected at baseline were present in TCGA. Tumor purity from collected swabs correlated with MRI tumor volumes during the course of treatment (R2=0.969). CDK4/CDK6/cyclin D1-related gene mutations involved in the ERK1/2, p16INK4, and p53 pathway and G1/S checkpoint most commonly persisted at the end of CRT. ConclusionThis non-invasive swab technique to serially sample tumor during CRT will allow new discoveries of dynamic tumor mutational profile changes during chemoradiation for mucosal tumors. Mutations that survived or increased during the initial weeks of radiation treatment are potential drivers of radiation resistance including the CDL4/CDK6/cyclin D1-related pathway. Statement of Translational RelevanceThere are no established biomarkers to predict chemoradiation (CRT) response for cervical cancer patients. Serial biopsies cannot be performed due to risks of bleeding and fistula. We used a novel non-invasive swab-based biopsy technique to obtain serial samples from a cohort of twenty-seven patients through the course of treatment, and validated this approach to obtain whole exome sequencing data. We analyzed dynamic tumor mutation profiles during CRT. Results from this study show that mutations in CDK4/CDK6/cyclin D1-related genes increased at the end of CRT, suggesting this pathway as a potential driver of radiation resistance.

cancer biology↗