Evaluation of Tumor and Blood Immune Biomarkers in Resected Non-small Cell Lung Cancer

Investigating tumor infiltrating lymphocytes in Non-small Cell Lung Cancer (NSCLC) is of
clinical importance for multiple reasons. Cellular, antigen, and cytokine profiles associated
with favorable clinical outcomes after therapy are currently lacking in lung cancer, and
these results may lead to the development of clinically important prognostic and predictive
biomarkers. Additionally, by determining the specific cell types and antigen targets of
effector cells in the microenvironment, strategies can be devised to alter mechanisms
regulating tumor immune tolerance. These data may ultimately enable future, novel
combinational approaches of anti-tumor therapies through early phase clinical trials designed
to improve clinical outcomes for patients with lung cancer. Finally, by correlating
immunologic profiles with clinical outcomes (including pathologic response and progression
free survival), signatures can be derived to help predict benefit from cytotoxic chemotherapy
for patients receiving these treatments.

This study will plan to enroll a total of 30 patients. This number will consist of a
combination of early stage NSCLC patients receiving no neoadjuvant therapy, standard
neoadjuvant cytotoxic chemotherapy, or immune checkpoint therapy as well as patients with
metastatic disease undergoing tumor resection that have received prior systemic therapy of
interest, including but not limited to anti-PD1/PDL agents.

Standard diagnostic and staging work up will be performed, including pathologic/histologic
diagnosis of cancer. Patients will receive therapy as deemed appropriate by their treating
physician as per standard clinical care or as part of a clinical cancer trial. There is no
randomization nor stratification. Patients will not receive any information about the
assays/research performed as these are for research purposes only.

Data from patients will be extracted from medical records and images. Data elements that will
be extracted include the following: age, sex, tumor histology and stage, chemotherapy
regimens and immune-modulating therapy dose and schedule, disease response (outcomes).

Tumor specimen samples will be collected at the time of definitive surgical resection of
tumor. After the specimen has been processed for margin status and the frozen section
assessment of the specimen is complete, a specimen of excess tumor (at least 1gm) will be
released and acquired by the tumor immunology correlative science staff for isolation of
tumor infiltrating lymphocytes for purposes of this protocol with any remaining tissue to be
processed by the Duke Biorepository staff if the subject has consented to biobanking. For
those subjects that decline participation in this biorepository tissue will be processed as
outlined above.

Blood will be collected prior to surgery to assess activated CD8+ T cells with specificity
against tumor antigens and CD4 and CD8 functional memory.

Inclusion Criteria:

- Planned standard of care surgical resection, T > 3 cm or metastatic tumor >1 cm

- Age 18 or older

- Signed written ICF

- If neoadjuvant treatment is received, regimens containing either platinum-based
chemotherapy or anti-PD1/PDL1 treatment will be allowed.

- Patients with metastatic disease undergoing tumor resection will be eligible if prior
treatment has included systemic therapy of interest, including, but not limited to,
anti-PD1/PDL agents.

Exclusion Criteria:

- Prisoners or subjects who are compulsorily detained for treatment of either
psychiatric or physical (e.g. infectious) illness are not eligible.