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Phagocytosis
Cieniewicz B, Bhatta, A, Torabi, D, Corey, D. Chimeric TIM-4 receptor-modified T cells targeting phosphatidylserine mediates both cytotoxic anti-tumor responses and phagocytic uptake of tumor-associated antigen for T cell cross presentation. Molecular Therapy. 2023.
Caronni N, Piperno GM, Simoncello F, Romano O, Vodret S, Yanagihashi Y, Dress R, Dutertre CA, Bugatti M, Bourdeley P, Del Prete A, Schioppa T, Mazza EMC, Collavin L, Zacchigna S, Ostuni R, Guermonprez P, Vermi W, Ginhoux F, Bicciato S, Nagata S, Benvenuti F. TIM4 expression by dendritic cells mediates uptake of tumor-associated antigens and anti-tumor responses. Nat Commun. 2021; 12: 2237.
Ravichandran KS. Find-me and eat-me signals in apoptotic cell clearance: progress and conundrums.
J Exp Med. 2010 Aug 30; 207(9): 1807–1817.
Toda S, Hanayama R, and Nagata S. Two-Step Engulfment of Apoptotic Cells. Mol Cell Biol. 2012 Jan;32(1):118-25.
Norimoto Kobayashi1, Piia Karisola, Victor Peña-Cruz, David M Dorfman, Masahisa Jinushi, Sarah E Umetsu, Manish J Butte, Haruo Nagumo, Irene Chernova, Baogong Zhu, Arlene H Sharpe, Susumu Ito, Glenn Dranoff, Gerardo G Kaplan, Jose M Casasnovas, Dale T Umetsu, Rosemarie H Dekruyff, Gordon J Freeman TIM-1 and TIM-4 glycoproteins bind phosphatidylserine and mediate uptake of apoptotic cells. Immunity 2007 Dec;27(6):927-40.
Phosphatidylserine biology and targeting
Dirk BS., Weir G, Quinton T, Hrytsenko O, and Stanford MM. Combination of a T cell activating therapy and anti-phosphatidylserine enhances anti-tumour immune responses in a HPV16 E7-expressing C3 tumour model. Sci Rep. 2021; 11: 4502.
Budhu S, Giese R, Gupta A, Fitzgerald K, Zappasodi R, Schad S, Hirschhorn D, Campesato LF, De Henau O, Gigoux M, Liu C, Mazo G, Deng L, Barker CA, Wolchok JD, and Merghoub T. Targeting phosphatidylserine enhances the anti-tumor response to tumor-directed radiation therapy in pre-clinical model of melanoma. Cell Rep 2021; 34(2): 108620.
Schad S, Hirschhorn-Cymerman D, Budhu S, Zhong H, Yang X, Merghoub T, and Wolchok JD. Phosphatidylserine targeting antibody enhances anti-tumor activity of adoptive cell therapies in a mouse melanoma model. J Immunol 2020, 204 (1 Supplement) 170.5.
Nagata S, Suzuki J, Segawa K, and Fugii T. Exposure of phosphatidylserine on the cell surface. Cell Death and Differentiation 2016; 23: 952–961.
Borisenko GG, Matsura T, Liu S-X, Tyurin VA, Jianfei J, Serinkan FB, Kagan VE. Macrophage recognition of externalized phosphatidylserine and phagocytosis of apoptotic Jurkat cells–existence of a threshold. Arch Biochem Biophys 2003;413(1):41-52.
Professional antigen presentation by activated T cells
Lanzavecchia A, Roosnei E, Gregory, T, Berman P, and Abrignani S. T cells can present antigens such as HIV gp120 targeted to their own surface molecules. Nature 1998; 334: 530-532.
Barnaba V, Watts C, de Boer M, Lane P, and Lanzavecchia A. Professional presentation of antigen by activated human T cells. Eur J Immunol 1994; 24(1):71-5.
Role of tumor in microenvironment
Fu C and Jiang A. Dendritic Cells and CD8 T Cell Immunity in Tumor Microenvironment
Front Immunol. 2018; 9: 3059.
Chen, Pei Hsuan. JCI Insight. 2020;5(12) Activation of CAR and non-CAR T cells in the tumor micro environment following CAR T cell therapy