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Page 8 of 11 Heft Neal et al. J Cancer Metastasis Treat 2019;5:76 I http://dx.doi.org/10.20517/2394-4722.2019.32

with Pembrolizumab (NCT02752074), was unfortunately halted after a similar trial in melanoma revealed
no improvement in overall or progression free survival with the addition of Epacadostat to pembrolizumab
[36]
compared to the control arm .
[78]
Additional therapies targeting immunosuppressive cytokines have also been developed . Current
trials investigating antagonists of TNF receptor aims to inhibit Treg activity and are being tested both as
monotherapy and in combination with anti-PD-1 therapies in HNSCC (NCT02740270, NCT02274155).

The final step in the cancer immunity cycle involves tumor cell death induced by activated CTLs. The ideal
immunotherapy would bypass the preceding steps and provide T cells already primed to patient specific
antigens. This has been successful in hematologic malignancies with therapies such as CAR-T and multiple
[79]
ongoing clinical trials are investigating the use of T-cell therapies in solid malignancies as well . A
clinical trial investigating the use of adoptive T cell transfer in HPV mediated disease in currently ongoing
(NCT03578406). A previous study has shown some promise in seven patients with head and neck cancer (5
[80]
with SCC, 1 with melanoma and 1 with spindle cell sarcoma) .

There are also ongoing trials assessing unique approaches that target multiple aspects of the immune
cycle. MVX-ONCO-1 is a treatment that involves subcutaneous injection of capsules containing immune-
modulatory granulocyte-macrophage colony stimulating factor and irradiated tumor cells with the aim of
stimulating a tumor specific immune response (NCT02999646).

CONCLUSION
HNSCC represents a diverse group of diseases and exhibits varying degrees of immune dysregulation.
Traditional therapeutic approaches are curative in 50% of patients and have proven to have
immunomodulatory effects. Currently approved immunotherapies have shown some promise but
unfortunately only a small fraction of patients benefit. This review summarizes the most common immune
disruptions identified in head and neck cancer and discusses ongoing approaches aimed at targeting the
tumor immune microenvironment.

DECLARATIONS
Authors’ contributions
Conceptualization, data curation, writing, review/editing: Heft Neal ME
Writing, review/editing: Haring CT
Writing, review/editing: Mann JE
Supervision, review/editing: Brenner JC
Conceptualization, writing, review/editing: Spector ME
Conceptualization, writing, review/editing: Swiecicki PL

Availability of data and materials
Not applicable.

Financial support and sponsorship
Heft Neal ME was supported in part by the NIH Grant (T32 DC005356). Brenner JC was supported in part
by American Cancer Society Grant: 132034-RSG-18-062-01-TBG. Brenner JC was supported by F31: DE-
027600-01.

Conflicts of interest
All authors declared that there are no conflicts of interest.