Project Details
Description
Treatment options for surgically inoperable or metastatic salivary gland cancer
are restricted to chemotherapy. To date immunotherapy that includes immune checkpoint
inhibitors like Pembrolizumab and Nivolumab are not approved by FDA for the management
of salivary gland cancer. KEYNOTE-028 (NCT02054806) showed objective response rate
of 12% with a 4-month median duration of response and overall response rate of nivolumab
was 4%. Salivary gland adenoid cystic carcinoma (ACC) is known as an immune cold
tumour, contrastingly mucoepidermoid carcinoma (MEC) of the salivary gland is considered
immune hot tumour. The ACC tumour microenvironment (TME) exhibits 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. Our preliminary data suggest significantly low expression of Annexin A3 (ANXA3) in ACC compared to MEC. These results are in accordance with the previous findings that suggest high expression of ANXA3 promotes
immune infiltration and improves tumour prognosis. We, therefore, hypothesise that
overexpression of Annexin A3 using functionalized nanoparticle will convert ACC into an
immune hot tumour.
are restricted to chemotherapy. To date immunotherapy that includes immune checkpoint
inhibitors like Pembrolizumab and Nivolumab are not approved by FDA for the management
of salivary gland cancer. KEYNOTE-028 (NCT02054806) showed objective response rate
of 12% with a 4-month median duration of response and overall response rate of nivolumab
was 4%. Salivary gland adenoid cystic carcinoma (ACC) is known as an immune cold
tumour, contrastingly mucoepidermoid carcinoma (MEC) of the salivary gland is considered
immune hot tumour. The ACC tumour microenvironment (TME) exhibits 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. Our preliminary data suggest significantly low expression of Annexin A3 (ANXA3) in ACC compared to MEC. These results are in accordance with the previous findings that suggest high expression of ANXA3 promotes
immune infiltration and improves tumour prognosis. We, therefore, hypothesise that
overexpression of Annexin A3 using functionalized nanoparticle will convert ACC into an
immune hot tumour.
| Status | Active |
|---|---|
| Effective start/end date | 1/10/25 → 30/09/27 |