TY - UNPB
T1 - Functionalized nanoparticle transforms cold to hot adenoid cystic carcinoma of salivary gland tumour microenvironment in vitro
AU - Chakraborty, Rajdeep
AU - Shah, Ria
AU - Chien, Arthur
AU - Akter, Masuma
AU - Amirkhani, Ardeshir
AU - Winn, Thiri
AU - Shen, Chao
AU - Shahbazi, Mohammad-Ali
AU - Tukova, Anastasiia
AU - Shannon, Kerwin
PY - 2026/4/21
Y1 - 2026/4/21
N2 - Adenoid cystic carcinoma (ACC) of salivary gland is an immune-cold tumour. Annexin A3 (ANXA3) is an apoptotic protein found to be participating in immune cell infiltration in tumour microenvironment (TME) of various cancer cases. Significant low expressions of ANXA3 protein found in adenoid cystic carcinoma. We hypothesized overexpressing ANXA3 transforms ACC cold TME to hot. We cultured UM-HACC-2A and UFH2 spheroids on extracellular matrix and co cultured them with peripheral blood mononuclear cells. We functionalized FDA (The Food and Drug Administration) approved Poly(lactic-co-glycolic acid) PLGA nanoparticles with anti-cMyb antibody and ANXA3 recombinant protein using streptavidin-biotin conjugation. Upon overexpressing ANXA3 in ACC spheroids in immune coculture model using functionalized nanoparticles, significant increase of tumour infiltrating lymphocytes and decrease in the size of the ACC spheroids observed. Apoptotic profiler assay further confirmed significant upregulation of apoptotic proteins, some of them participate in immune infiltration. Overall, this project exhibits promising results showing potential approach to convert ACC into an immune hot tumour.
AB - Adenoid cystic carcinoma (ACC) of salivary gland is an immune-cold tumour. Annexin A3 (ANXA3) is an apoptotic protein found to be participating in immune cell infiltration in tumour microenvironment (TME) of various cancer cases. Significant low expressions of ANXA3 protein found in adenoid cystic carcinoma. We hypothesized overexpressing ANXA3 transforms ACC cold TME to hot. We cultured UM-HACC-2A and UFH2 spheroids on extracellular matrix and co cultured them with peripheral blood mononuclear cells. We functionalized FDA (The Food and Drug Administration) approved Poly(lactic-co-glycolic acid) PLGA nanoparticles with anti-cMyb antibody and ANXA3 recombinant protein using streptavidin-biotin conjugation. Upon overexpressing ANXA3 in ACC spheroids in immune coculture model using functionalized nanoparticles, significant increase of tumour infiltrating lymphocytes and decrease in the size of the ACC spheroids observed. Apoptotic profiler assay further confirmed significant upregulation of apoptotic proteins, some of them participate in immune infiltration. Overall, this project exhibits promising results showing potential approach to convert ACC into an immune hot tumour.
U2 - 10.64898/2026.04.18.719423
DO - 10.64898/2026.04.18.719423
M3 - Preprint
T3 - bioRxiv
BT - Functionalized nanoparticle transforms cold to hot adenoid cystic carcinoma of salivary gland tumour microenvironment in vitro
ER -