44CT – Understanding Oral Cavity Microbiome and Tumor Microenvironment Cross-talk

Status: Filled – Intern: Payal Patel
Intern: Payal Patel
Faculty Name: carissa-m-thomas-md-phd
UAB Department: Department of Otolaryngology – Head and Neck Surgery
UAB School: UAB School of Medicine
Campus Address: 1155 Faculty Office Towers (510 20th Street South) and Volker Hall (1670 University Blvd)
Telephone Number: (713) 515-2852
Email: carissathomas@uabmc.edu or Click to Send E-Mail
For how many summers have you served as a preceptor: 0
CCC Research Area: Inflammation, Immunology, and Immunotherapeutics
Number of hours per week that the preceptor will personally supervise or work with the intern: 20
Other faculty, staff, or graduate students who may help to supervise the intern:
1. Dr. Jason Warram
2.
Title of Project: 44CT – Understanding Oral Cavity Microbiome and Tumor Microenvironment Cross-talk
Project Description:

The human microbiome has been found to play an important role in carcinogenesis in a number of cancers. Certain bacteria within the microbiome may modulate the local and systemic immune system and tumor microenvironment (TME) to promote or inhibit tumor progression and metastases. The oral cavity has an extensive mucosal microbiome (700 taxa) that has not been well characterized in oral cavity squamous cell carcinoma (OCSCC). In OCSCC, increased peritumoral inflammation is associated with decreased metastases and increased recurrence free survival. There may be a link between the mucosal microbial community and peritumoral inflammation in OCSCC. If we knew candidate bacterial drivers that modulate inflammation, we could modify the microbiome, peritumoral inflammation and TME to create a more favorable phenotype. Our hypothesis is the oral microbiome in OCSCC is stable over time and influences the peritumoral inflammatory infiltrate and subsequent cytokine production and PD-L1 expression. We aim to delineate a map of the mucosal microbiome of OCSCC and to correlate that map with histologic features of the tumor. A patient-derived OCSCC organoid model system will be used to study bacteria-induced changes in cytokine production and PD-L1 expression. This will lay the foundation for understanding interactions between bacteria, the immune system, and TME. We will answer these questions with the following specific aims:

(a) AIM 1. Characterize the microbiome within different subsites of OCSCC to understand the heterogeneity of the microbiome and to assess microbiome stability over time.

(b) AIM 2. Characterize the microbiome of OCSCC compared to the contralateral uninvolved side to discover potentially important bacterial drivers of the peritumoral inflammatory infiltrate.

(c) AIM 3. Establish OCSCC organoids co-cultured with macrophages to understand microbiome-induced alterations in cytokine production and PD-L1 expression.

The CaRES intern will focus primarily on aim 3 and gain important skills in cell culture and flow cytometry. They will use a human tongue squamous cell carcinoma cell line to establish organoids. Flow cytometry will be used to assess baseline expression of PD-L1 on tumor cells. In addition, expression of PD-L1 on naïve macrophages and macrophages exposed to bacteria of interest will be assessed with flow cytometry. In addition, the CaRES intern will assist with microbiome sample collection from patients with OCSCC including administering patient surveys, performing oral swabs, peripheral blood collection, processing of peripheral blood, and fresh tumor collection from the operating room. There is the opportunity for the CaRES intern to observe head and neck cancer surgeries if interested.

Project Status: Will begin on or before the CaRES student’s start date
Location of Project: Birmingham, AL (UAB)
Proposed Start Date: May 4, 2020
Proposed End Date: August 28, 2020
Expected work schedule for intern: Not very flexible, intern MUST be at work on certain days of the week and at certain times of the day (as may be necessary to interview patients, attend lab meetings, process samples, etc.) and should contribute full-time effort.
Category of Project: Laboratory Research
Cancer topic: Head and Neck, Oral Cavity
Does this project involve human subjects: Yes
Does this project involve animal subjects: No
Duty:
1.

Culturing organoids using a human tongue squamous cell carcinoma cell line as well as culturing monocytes/macrophages.

2.

Flow cytometry of epithelial cells and monocytes/macrophages for PD-L1.

3.

Assisting with microbiome sample collection including peripheral blood collection and processing and transporting tumor tissue from the operating room to the lab. Will also assist with administering patient surveys.

Preceptor will provide intern with access to the following:
Office or desk space, Computer and printer, Laboratory work bench space, Supplies needed to complete project, Equipment needed to complete project
Likelihood that intern will be included as an author on one or more publications
related to this summer research project:
Very likely
Areas in which the ideal candidates will have experience:
Laboratory Skills, basic knowledge