A Prelude towards transforming adenoid cystic carcinoma into an immune hot tumour: Phase II

Salivary gland adenoid cystic carcinoma (ACC) is known as immune cold tumour,
contrastingly mucoepidermoid carcinoma (MEC) of salivary gland is considered immune hot
tumour. ACC tumour microenvironment (TME) exhibit very low infiltration of immune
cells. So far, apoptosis has been found to tune tumour immunity based on the demonstration
of apoptosis of immune cells (T effector cells), that undermines the anti-tumour reactivity of
immune cells in the tumour microenvironment. This eventually facilitates growth of T
regulatory cells, M2 macrophage, and myeloid derived suppressor cells.
Our preliminary data (unpublished) suggest significantly low expression of Annexin A3
(ANXA3) in ACC compared to MEC. Additionally, upon RNA-seq analysis of
transcriptomic data for ACC and normal salivary tissue samples, we found Annexin A3
(ANXA3) downregulated in ACC samples compared to its normal counterpart.
These results are in accordance with the previous findings that suggest high expression of
ANXA3 promotes immune infiltration and improves tumour prognosis, this might be one
of the possible reasons for MEC exhibiting an immune-hot TME, whereas ACC shows
contrasting features of immune-cold TME. We, therefore, hypothesise that overexpression
of Annexin A3 will convert ACC into an immune hot tumour.
We will determine ACC cell proliferation and apoptosis after overexpressing ANXA3, immune cell infiltration after overexpressing ANXA3, determine the effect of ANXA3 in ACC cells during the treatment of immune check point inhibitors, and cell surface glycosylation alteration during progression of ACC and if any link to Annexin proteins.

This project is about overexpressing a protein called ANXA3. Its expression is very less in salivary gland cancer (Adenoid Cystic Carcinoma [ACC]). We hypothesise that if we increase the expression of this protein, it will turn ACC tumour from a cold tumour (lack of immune cells) to a hot tumour (increase immune cells). To date, no drugs are working in ACC. If we can turn the tumour into a hot tumour, drugs might start working. It is like increasing the flow of blood inside the tumour!

This project will act as a prelude to the future development of an Annexin A3 engineered
antibody that might be concomitantly or sequentially administered along with immunotherapy
for the improved treatment of salivary gland adenoid cystic carcinoma.