Immune profiling of tumor and blood of patients with nasopharyngeal cancer

Nasopharyngeal carcinoma (NPC) is highly prevalent in southeast Asia.
Chemoradiation (CR) is currently the primary treatment modality for locally
advanced disease. However, approximately 40% of the patients develop recurrent
NPC.
Undifferentiated NPC is commonly associated with Epstein Barr virus which can
cause dysregulation of the NF-Kb pathway leading to an inflammatory response in
NPC . However recurrent NPC patients upregulate immunosuppressive mechanisms to
downregulate the immune response to NPC. In order to develop better therapeutic
strategies, it is a prerequisite to perform in-depth analysis of systemic
(i.e., blood) as well as local (i.e., tissue) immune markers of NPC patients
treated with CR. These analyses could reveal immune-suppressive mechanisms
employed by NPC that can provide potential targets for immunomodulatory drugs
to be used in combination with CR to enhance its clinical efficacy.

To determine local and systemic immune markers, with emphasis on T lymphocytes,
in primary and recurrent NPC patients and investigate how these immune markers
correlate to clinical response to CR in NPC.
Primary Objective1:
Profile whole blood and PBMCs of NPC patients who are undergoing CR treatment
for immune cell numbers and phenotype (with emphasis on T cell subsets).
Second Objective(s):
Profile tumor tissue of NPC patients who are undergoing CR treatment for ICD,
type I IFNs and T cell evasion.
Third Objective(s):
Correlate systemic as well as local immune markers to clinical outcomes like
recurrence free survival.
Fourth Objective(s):
Profile plasma (immune mediators and EBV titers) and PBMCs (T cell functions
and TCR repertoire) of NPC patients who undergo CR treatment, and correlate
these markers to above-mentioned immune markers, clinical outcomes and EBV
titers.

All patients with confirmed NPC diagnosis will be treated with 35 fractions of
2 Gy radiotherapy and 7 weekly cycles of 40 mg/m2 cisplatin. Patients will be
followed for 2 years. Blood is collected at the time of diagnosis, and at
different time points during treatment and follow up. Tissue is collected
during confirmatory biopsy and during follow up in case of recurrence or
residual disease. Whole blood and cryopreserved PBMCs are being used to perform
multiplex flow cytometry analysis. Tumor tissues will be processed into FFPE
samples for immunofluorescence. Plasma of NPC patients will be used to isolate
EBV DNA and measure chemokine expression using ELISA.

The current study does not pose any risk to the patients, and the only burden
is collection of additional blood during (already scheduled) blood collections
and an additional biopsy during diagnostic biopsy. The study has no direct
benefit for the included subjects. However, the results of this study are
expected to lead to optimization of therapeutic strategies for NPC patients in
the future.