Memory Phenotype in Oral Cancer

Squamous cell carcinoma of the head and neck (HNSCC) is the sixth most common neoplasm in the
world and despite advances in treatment, the 5-year survival remains approximately 50%.
Because of the need for new therapies, the possibility of immunotherapeutic approaches for
HNSCC patients has gained interest. Interest in this has continued as more than half of the
subjects enrolled to an ongoing clinical trial in patients with with oral squamous cell
carcinoma (OCSCC) have responded to neoadjuvant presurgical Nivolumab therapy. Additionally,
unlike other solid tumors it appears responders have higher proportions of CD4+
tumor-infiltrating lymphocytes (TILs) whereas non-responders have an increase in CD8+ TILs
population. Furthermore, the investigator's data suggests that response to PD-1 blockade is
associated with an increase in CD45RA- CD62L+ population or central memory phenotype within
TIL whereas progression of disease correlates with an increase in the CD45RA- CD62L-
population or effector memory phenotype.

As previously demonstrated in several other tumor types the magnitude of response to
immunotherapy directly correlates to presence of antigen specific T cells within the tumor
and tumor microenvironment. Therefore, the long-term objective of this project is to identify
predictive biomarkers of immune response from either TILs or tumor cells from patients with
head and neck squamous carcinoma. To achieve this goal the overall objective of the current
study is to develop a pre-clinical murine models in an effort to more completely evaluate the
memory phenotype of TILs before and after PD-1 inhibition and to subsequently to determine
the efficacy of TIL therapy in this mouse model of oral cancer. This project will test a
central hypothesis that TILs derived from responders to neoadjuvant pre-surgical PD-1
inhibition in both a patient derived xenograft mouse model of oral cancer.

Inclusion Criteria:

- Newly diagnosed histologically proven locoregional oral squamous cell carcinoma (OSCC)
without evidence of distant metastases. OSCC includes the subsites of oral tongue,
floor of mouth, gingiva, retromolar trigone and buccal mucosa OR

Recurrent or persistent histologically proven locoregional OSCC that was initially treated
with surgery alone.

- must be eligible for surgical resection

- greater than 18 years of age

Exclusion Criteria:

- prior immunotherapy or treatment with another anti PD-1 agent besides nivolumab

- prior chemotherapy including cetuximab or radiation therapy

- concomitant malignancies except cutaneous squamous cell carcinoma or basal cell
carcinoma

- unresectable primary tumor or regional disease or distant metastases