Immunogenic cancer cell death selectively induced by near infrared photoimmunotherapy initiates host tumor immunity.

Mikako Ogawa,Jane B Trepel,Hari Shroff,Saori Tomita,Toyohiko Yamauchi,Timothy Haystead,Peter L Choyke,Yusuke Tomita,Min-Jung Lee,Tadanobu Nagaya,Hisataka Kobayashi,Yuko Nakamura,Sunmin Lee,Hidenao Iwai,Kazuhide Sato,Abhishek Kumar

doi:10.18632/oncotarget.14425

Abstract

Immunogenic cell death (ICD) is a form of cell death that activates an adaptive immune response against dead-cell-associated antigens. Cancer cells killed via ICD can elicit antitumor immunity. ICD is efficiently induced by near-infrared photo-immunotherapy (NIR-PIT) that selectively kills target-cells on which antibody-photoabsorber conjugates bind and are activated by NIR light exposure. Advanced live cell microscopies showed that NIR-PIT caused rapid and irreversible damage to the cell membrane function leading to swelling and bursting, releasing intracellular components due to the influx of water into the cell. The process also induces relocation of ICD bio markers including calreticulin, Hsp70 and Hsp90 to the cell surface and the rapid release of immunogenic signals including ATP and HMGB1 followed by maturation of immature dendritic cells. Thus, NIR-PIT is a therapy that kills tumor cells by ICD, eliciting a host immune response against tumor.

Highlights

Immunogenic cell death (ICD), which involves changes in the composition of the cell surface and release of soluble mediators, was initially described by Zitvogel and Kroemer et al [1,2,3]
When hypermolar 50 mM dextran was added to the solution, cell swelling was not observed after NIR light exposure as it was not possible for water to flow into cells under this condition (Figure 1Ac, Supplementary Video 3)
After exposing cells previously incubated with the antibody-photosensitizer conjugate (APC) to NIR light, ionic pressure gradients across the cellular membrane were impaired due to damage to the plasma membrane that resulted in cell swelling followed by cell bursting

Summary

Introduction

Immunogenic cell death (ICD), which involves changes in the composition of the cell surface and release of soluble mediators, was initially described by Zitvogel and Kroemer et al [1,2,3]. ICD relies on the generation of immunogenic signals induced by a variety of stimuli, including damage-associated molecular patterns (DAMPs) such as the endoplasmic reticulum (ER) chaperone calreticulin, ATP, high mobility group box 1 (HMGB1), heat shock protein (Hsp), and Hsp90 [4, 5]. These signals activate dendritic cells (DCs) to stimulate the presentation of tumor-antigens to T-cells. Microscopy during NIR-PIT reveals rapid bleb formation on the cell membrane within minutes of exposure to light [8]

Methods

Results

Conclusion