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Publications (323)
Background
Appendiceal cancer’s mucinous nature and scant cellularity significantly restrict traditional molecular analyses. Single cell sequencing overcomes technical challenges of bulk sequencing but lacks spatial information. To address this, we employed digital spatial profiling to select regions of interest exclusive of mucin pools to better i...
Background
Mucosal melanoma (MM) is a rare melanoma subtype with distinct biology¹ and low response rates to immune checkpoint inhibitors (ICIs).2 3 The biology of MM is poorly understood. We sought to prospectively, uniformly, and comprehensively profile a cohort of MM patients to determine the interplay of gut, mucosal and tumor microbiome on ICI...
Background
Integrating the uniquely multi-platform data of the ImmunogenomiC PrOfiling of Non-small cell lung cancer (NSCLC) Project (ICON) study and NEOSTAR trial presents an invaluable opportunity to comprehensively examine how neoadjuvant chemoimmunotherapy modulates NSCLC across scales. We developed a generalizable integration and analysis fram...
Background
Despite significant advances in understanding the role of microbiome in cancer and tumor immunity, the impact of microbiome in primary and metastatic brain tumors remains largely unknown. Elucidating the dynamic interaction between microbial entities and the brain tumor microenvironment can provide novel microbiome-based opportunities to...
Background
The association of dietary fiber intake with gut microbiome profiles and improved immune checkpoint blockade (ICB) response is well-described in melanoma patients. Higher social vulnerability index (SVI) has also been associated with decreased gut microbiome diversity.4–9 We hypothesized that higher SVI and low food access (LFA) would be...
Background
The gut microbiome has been associated with response to anti-PD-1 therapy in melanoma, lung cancer, and kidney cancer. Small clinical trials combining gut microbiome modulation via fecal microbiota transplantation (FMT) and anti-PD-1 therapy showed promising results in melanoma patients. However, the mechanisms driving the gut microbiome...
Background
Undifferentiated pleomorphic sarcoma (UPS) is a common soft tissue sarcoma (STS) subtype associated with poor prognosis. We and others have shown that the sarcoma tumor immune microenvironment (TME) is highly variable both across and within STS histologies, and heavily influences response and resistance to immunotherapies. Using spatial...
Patients undergoing immune effector cell therapy (IECT) are at high risk for infections. We assessed seropositivity against pneumococcus, tetanus, and diphtheria in patients before and after IECT and the patients’ response to vaccination. We enrolled patients who underwent IECT from January 2020 to March 2022. Antibody levels for diphtheria, tetanu...
Accumulating evidence indicates that the gut microbiome influences cancer progression and therapy. We recently showed that progressive changes in gut microbial diversity and composition are closely associated with tobacco-associated lung adenocarcinoma (LUAD) in a human-relevant mouse model. Furthermore, we demonstrated that the loss of the antimic...
Mexican Americans are disproportionally affected by metabolic dysfunction-associated steatotic liver disease (MASLD), which often co-occurs with diabetes. Despite extensive evidence on the causative role of the gut microbiome in MASLD, studies determining the involvement of the gut phageome are scarce. In this cross-sectional study, we characterize...
Adenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited. We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues using 16S rRNA gene se...
Motivation
Although the human microbiome plays a key role in health and disease, the biological mechanisms underlying the interaction between the microbiome and its host are incompletely understood. Integration with other molecular profiling data offers an opportunity to characterize the role of the microbiome and elucidate therapeutic targets. How...
Motivation: Although the human microbiome plays a key role in health and disease, the biological mechanisms underlying the interaction between the microbiome and its host are incompletely understood. Integration with other molecular profiling data offers an opportunity to characterize the role of the microbiome and elucidate therapeutic targets. Ho...
Background: Gut microbiota modulation shows promise in improving immune checkpoint blockade (ICB) response; however, precision biomarker-driven trials using rationally-designed consortia are lacking. To address this, we performed a multi-center, randomized placebo-controlled, biomarker-stratified phase 1 trial in patients with ICB-naïve unresectabl...
Gut-microbiota modulation shows promise in improving immune-checkpoint blockade (ICB) response; however, precision biomarker-driven, placebo-controlled trials are lacking. We performed a multicenter, randomized placebo-controlled, biomarker-stratified phase I trial in patients with ICB-naïve metastatic melanoma using SER-401, an orally delivered Fi...
Introduction MM is a rare melanoma subtype with distinct biology, low immunogenicity and tumor mutational burden, and subsequently lower response rates to ICIs. The biology of MM is poorly understood. We sought to prospectively, uniformly, and comprehensively profile a cohort of MM patients to determine the interplay of molecular variation, germlin...
Introduction: Metastatic brain tumors are associated with significant morbidity and mortality. The microbiome has emerged as a novel hallmark of cancer, with a prominent role in tumor immunity and response to treatment. However, the role of the microbiome in brain tumors, and in particular brain metastasis, is largely unknown. We hypothesized that...
Background: Distinct gut microbiome signatures are associated with response, resistance, and toxicity to immune checkpoint blockade (ICB). Fecal microbiome transplants (FMT) have validated the importance of the gut microbiome in enhancing response and overcoming resistance to immunotherapy. However, donor selection remains a key challenge for FMT....
Background: Perioperative antibiotic prophylaxis is routinely utilized to reduce surgical site infections (SSIs). However, the rate of SSIs following a clean surgical procedure is <3%. Overuse of antibiotics is associated with potential adverse effects, including disruption of the composition and function of the native gut microbiota. Numerous stud...
Background:Previous studies have shown that intratumoral immune aggregates called tertiary lymphoid structures (TLS) are associated with exceptional response to immune checkpoint blockade (ICB) in several cancer types. However, the specific mechanisms through which TLS contribute to ICB-response remain poorly characterized in part due to technical...
Background: Patients with small bowel neuroendocrine tumors (SBNET) frequently present with metastatic disease and the efficacy of available therapies, including immune checkpoint blockade (ICB), is limited. Toward developing novel immunomodulatory strategies, we interrogated the tumor immune microenvironment of SBNETs using bulk transcriptional an...
Disruption of the intestinal microbiome is observed with acute graft-versus-host disease (GVHD) of the lower gastrointestinal (LGI) tract and fecal microbiota transplantation (FMT) has successfully cured steroid-refractory cases. In this open-label, single-arm, pilot study (NCT04139577), third-party, single donor FMT was administered in combination...
Background: Adenoid cystic carcinoma (ACC) is a rare, usually slow-growing yet aggressive head and neck malignancy. Despite its clinical significance, our understanding of the cellular evolution and microenvironment in ACC remains limited.
Methods: We investigated the intratumoral microbiomes of 50 ACC tumor tissues and 33 adjacent normal tissues u...
Background
Adenoid 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.
Methods
We investigated the intratumoral microbiome of 50 ACC tumors and 33 adjacent normal tissues using 16S rRNA gen...
160
Background: Given the increasing incidence of young onset rectal cancer (YORC) in recent decades, we examined the potential of tumor and fecal microbiome pathways in YORCs as compared to late-onset rectal cancers (LORCs) while also exploring markers of response to neoadjuvant therapy (NAT). We hypothesize microbial markers reflect unique and po...
596
Background: Patients with small bowel neuroendocrine tumors (SBNET) frequently present with metastatic disease, and efficacy of available therapies, including immune checkpoint inhibitors (ICI), is limited. Toward developing novel immunomodulatory strategies, we evaluated the tumor immune microenvironment of SBNETs using bulk transcriptional an...
Background: Accessible prebiotic foods hold strong potential to jointly target gut health and metabolic health in high-risk patients. The BE GONE trial targeted the gut microbiota of obese surveillance patients with a history of colorectal neoplasia through a straightforward bean intervention.
Methods: This low-risk, non-invasive dietary intervent...
Although the genetic basis and pathogenesis of type 1 diabetes have been studied extensively, how host responses to environmental factors might contribute to autoantibody development remains largely unknown. Here, we use longitudinal blood transcriptome sequencing data to characterize host responses in children within 12 months prior to the appeara...
Tumor-resident Lactobacillus iners confer chemoradiation resistance through lactate-induced metabolic rewiring Graphical abstract Highlights d L. iners is associated with poor tumor response to chemoradiation d L. iners primes tumor metabolism for increased L-lactate production d Other lactic acid bacteria are associated with poor survival in other...
Motivation
Although the human microbiome plays a key role in health and disease, the biological mechanisms underlying the interaction between the microbiome and its host are incompletely understood. Integration with other molecular profiling data offers an opportunity to characterize the role of the microbiome and elucidate therapeutic targets. How...
Importance:
The gut microbiome modulates the immune system and responses to immunotherapy in patients with late-stage melanoma. It is unknown whether fecal microbiota profiles differ between healthy individuals and patients with melanoma or if microbiota profiles differ among patients with different stages of melanoma. Defining gut microbiota prof...
Objective:
External exposures, the host, and the microbiome interact in oncology. We aimed to investigate tumoral microbiomes in young-onset rectal cancers for profiles potentially correlative with disease etiology and biology.
Summary background data:
Young-onset rectal cancer is rapidly increasingly, with one in four new rectal cancer cases oc...
2568
Background: A major barrier to understanding the role of viruses in cancer progression has been the lack of sensitivity of current tools to assemble viral genomes in an untargeted way. Here, we utilize our novel VirMAP algorithm to identify eukaryotic and prokaryotic viruses associated with cancers, using RNA sequencing data from The Cancer Ge...
TPS9609
Background: Gut microbiome modulation is a promising strategy to enhance response to ICB Fecal microbiota transplant studies have shown positive signals of improved outcomes in both ICB naïve and refractory melanoma; however, this strategy is challenging to scale. Diet is a key determinant of the gut microbiota and we have previously shown...
The family Tymoviridae comprises positive-sense RNA viruses, which mainly infect plants. Recently, a few Tymoviridae-like viruses have been found in mosquitoes, which feed on vertebrate sources. We describe a novel Tymoviridae-like virus, putatively named, Guachaca virus (GUAV), isolated from Culex pipiens and Culex quinquefasciatus species of mosq...
Background: A major barrier to understanding the role of viruses in cancer progression has been the lack of sensitivity of current tools to identify and assemble viral genomes in an untargeted way. Here, we utilize our novel VirMAP algorithm to identify eukaryotic and prokaryotic viruses associated with cancers, using RNA sequencing data from The C...
Background
Squamous cell carcinoma of the anus (SCCA) is a rare gastrointestinal cancer. Factors associated with progression of HPV infection to anal dysplasia and cancer are unclear and screening guidelines and approaches for anal dysplasia are less clear than for cervical dysplasia. One potential contributing factor is the anorectal microbiome. I...
Neoadjuvant ipilimumab + nivolumab (Ipi+Nivo) and nivolumab + chemotherapy (Nivo+CT) induce greater pathologic response rates than CT alone in patients with operable non-small cell lung cancer (NSCLC). The impact of adding ipilimumab to neoadjuvant Nivo+CT is unknown. Here we report the results and correlates of two arms of the phase 2 platform NEO...
Background: The gut microbiome modulates response and resistance to immune checkpoint inhibitors (ICI) across different cancer types. The objective of this study was to explore the association between fecal microbiome profiles and clinical outcomes in patients with hormone receptor-positive (HR+) metastatic breast cancer (MBC) treated with eribulin...
Purpose:
Human papillomavirus (HPV) is the primary driver of cervical cancer. Though studies in other malignancies correlated peripheral blood DNA clearance with favorable outcomes, research on the prognostic value of HPV clearance in gynecological cancers using intratumoral HPV is scarce. We aimed to quantify the intratumoral HPV virome in patien...
IntroductionImmunotherapy is changing the standard of care in cancer treatment. Immune checkpoint blockers (ICBs) that block the checkpoint programs used by tumor cells to inhibit the immune response have been approved by the US Food and Drug Administration with varying efficacy across cancer types. Given the clear benefits of ICB in some patients,...
Immune checkpoint blockade (ICB) has revolutionized cancer treatment, yet quality of life and continuation of therapy can be constrained by immune-related adverse events (irAEs). Limited understanding of irAE mechanisms hampers development of approaches to mitigate their damage. To address this, we examined whether mice gained sensitivity to anti-C...
Purpose/Objective(s)
Infection with HPV is associated with vaginal microbiome alterations including higher abundance of Lactobacillus gasseri and Gardnerella vaginalis. Cervical dysbiosis is a risk factor for cervical cancer but less is known about the composition of the tumor microbiome of vaginal and vulvar cancers. In gynecological cancers, surg...
The gut microbiota shapes the response to immune checkpoint inhibitors (ICIs) in cancer, however dietary and geographic influences have not been well-studied in prospective trials. To address this, we prospectively profiled baseline gut (fecal) microbiota signatures and dietary patterns of 103 trial patients from Australia and the Netherlands treat...
The intestinal microbiota is an important modulator of graft-versus-host disease (GVHD), which often complicates allogeneic hematopoietic stem cell transplantation (allo-HSCT). Broad-spectrum antibiotics such as carbapenems increase the risk for intestinal GVHD, but mechanisms are not well understood. In this study, we found that treatment with mer...
Immunotherapies such as anti-CTLA-4 immune checkpoint blockade (ICB) have revolutionized cancer treatment, yet quality of life and continuation of therapy can be constrained by off-target tissue damage or immune-related adverse events (irAEs). At present, there is limited understanding of irAE mechanisms, hampering development of approaches to miti...
Background: The role of microbiome in different steps of tumor development and progression has been shown across various tumor types. However, the contribution of microbiome to brain tumors is yet to be understood. A crosstalk between the gut and oral microbiota and the brain microenvironment has been demonstrated in the context of neurological and...
Fungal infections are a major health problem that often begin in the gastrointestinal tract. Gut microbe interactions in early childhood are critical for proper immune responses, yet there is little known about the development of the fungal population from infancy into childhood. Here, as part of the TEDDY (The Environmental Determinants of Diabete...
Acute malnutrition, or wasting, is implicated in over half of all deaths in children under five and increases risk of infectious disease. Studies in humans and preclinical models have demonstrated that malnutrition is linked to an immature intestinal microbiota characterized by increased prevalence of Enterobacteriaceae. Observational studies in ch...
Opinion statement
In recent years, we have seen an increase in the study and interest of the role of the microbiome in the development of malignancies, their progression, and evasion of therapies. This has been particularly fruitful in the case of colorectal cancer; multiple investigators have described correlative observations as well as hypothese...
Purpose
Patients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options. Investigation into the microbiome's influence on treatment toxicity and its potential use as a predictive biomarker could improve these patients’ outcomes. Our study presents the first longitudina...
This study identifies a novel pathotype of cervical cancer-associated Lactobacillus iners ( L. iners ) that results in chemoradiation resistance in vitro and is associated with poor patient survival. Cervical cancer affects over half a million women a year around the world. Treatment for women with locally advanced cancer is delivered with definiti...
The gut-brain axis has presented a valuable new dynamic in the treatment of cancer and CNS diseases. However, little is known about the potential role of this axis in neuro-oncology. The goal of this review is to highlight potential implications of the gut-brain axis in neuro-oncology, in particular gliomas, and future areas of research. The gut-br...
Limited data exist on the spatial distribution of the colonic bacteria in humans. We collected the colonic biopsies from five segments of 27 polyp-free adults and collected feces from 13 of them. We sequenced the V4 region of the bacterial 16S rRNA gene using the MiSeq platform. The sequencing data were assigned to the amplicon sequence variant (AS...
Another benefit of dietary fiber
The gut microbiome can modulate the immune system and influence the therapeutic response of cancer patients, yet the mechanisms underlying the effects of microbiota are presently unclear. Spencer et al . add to our understanding of how dietary habits affect microbiota and clinical outcomes to immunotherapy. In an ob...
Background
Infectious complications in cancer patients (pts) who have received T-cell therapies are similar to those in autologous hematopoietic stem cell transplant (HCT) recipients, who - because they lose prior acquired immunity after undergoing conditioning regimens and transplantation- may be at an increased risk for vaccine-preventable infect...
Purpose/Objective(s)
Radiation therapy is curative for treating cervical, vaginal, and anal cancers, but can lead to gut toxicities that reduce quality of life in recovering patients. Previously, higher gut microbiome diversity was shown to be positively correlated with less severe acute gastrointestinal (GI) toxicities per patient-reported assessm...
Background
Despite the substantial advances in the treatment of systemic cancer, brain metastases are still responsible for significant morbidity and mortality, necessitating a better understanding of the mechanisms underlying this disease. Microbiota has emerged as a significant hallmark of cancer. Our group and others have demonstrated a prominen...
Metastatic melanoma is a deadly malignancy with poor outcomes historically. Immuno-oncology (IO) agents, targeting immune checkpoint molecules such as cytotoxic T-lymphocyte associated protein-4 (CTLA-4) and programmed cell death-1 (PD-1), have revolutionized melanoma treatment and outcomes, achieving significant response rates and remarkable long-...
Not all cancer patients with severe neutropenia develop fever, and the fecal microbiome may play a role. In neutropenic hematopoietic cell transplant patients (n=119), 63 (53%) developed a subsequent fever and had increased fecal Akkermansia muciniphila , a mucus-degrading bacteria (p=0.006, corrected for multiple comparisons).
In mouse models, two...
IMPORTANCE: Patients with localized squamous cell carcinoma of the anus (SCCA) who experience treatment toxicity or recurrences have few therapeutic options. Investigation into the microbiome's influence on treatment toxicity or its potential use as a predictive biomarker in this rare disease could improve these patients' outcomes.
OBJECTIVE: To lo...
Radiographic imaging is the standard approach for evaluating the disease involvement of lymph nodes in patients with operable NSCLC although the impact of neoadjuvant immune checkpoint inhibitors (ICIs) on lymph nodes has not yet been characterized. Herein, we present an ad hoc analysis of the NEOSTAR trial (NCT03158129) where we observed a phenome...
Treatment with combined immune checkpoint blockade (CICB) targeting CTLA-4 and PD-1 is associated with clinical benefit across tumor types, but also a high rate of immune-related adverse events. Insights into biomarkers and mechanisms of response and toxicity to CICB are needed. To address this, we profiled the blood, tumor and gut microbiome of 77...
Background: Despite the substantial advances in the treatment of systemic cancer, brain metastases are still responsible for significant morbidity and mortality. A better understanding of the mechanisms that facilitate brain metastasis formation can provide opportunities for the development of better diagnostics and therapeutics for this disease. M...
We examined the association between the colonic adherent microbiota and nocturnal sleep duration in humans. In a cross-sectional study, 63 polyp-free adults underwent a colonoscopy and donated 206 mucosal biopsies. The gut microbiota was profiled using the 16S rRNA gene sequencing targeting the V4 region. The sequence reads were processed using UPA...
e14566
Background: Immune checkpoint blockade (ICB) therapy transformed clinical oncology by inducing durable responses and increasing survival rates in many types of cancers. However, ICB is effective in only in a subset of patients. Recent studies delineated the role of gut microbiome as both a biomarker and a therapeutic in ICB responsiveness. W...
Background
A 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.
Materi...
Background
Next 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...
Diversity of the gut microbiome is associated with higher response rates for cancer patients receiving immunotherapy but has not been investigated in patients receiving radiation therapy. Additionally, current studies investigating the gut microbiome and outcomes in cancer patients may not have adjusted for established risk factors. Here, we sought...