MilliporeSigma
  • Home
  • Search Results
  • Tipping the immunostimulatory and inhibitory DAMP balance to harness immunogenic cell death.

Tipping the immunostimulatory and inhibitory DAMP balance to harness immunogenic cell death.

Nature communications (2020-12-09)
K Hayashi, F Nikolos, Y C Lee, A Jain, E Tsouko, H Gao, A Kasabyan, H E Leung, A Osipov, S Y Jung, A V Kurtova, K S Chan
ABSTRACT

Induction of tumor cell death is the therapeutic goal for most anticancer drugs. Yet, a mode of drug-induced cell death, known as immunogenic cell death (ICD), can propagate antitumoral immunity to augment therapeutic efficacy. Currently, the molecular hallmark of ICD features the release of damage-associated molecular patterns (DAMPs) by dying cancer cells. Here, we show that gemcitabine, a standard chemotherapy for various solid tumors, triggers hallmark immunostimualtory DAMP release (e.g., calreticulin, HSP70, and HMGB1); however, is unable to induce ICD. Mechanistic studies reveal gemcitabine concurrently triggers prostaglandin E2 release as an inhibitory DAMP to counterpoise the adjuvanticity of immunostimulatory DAMPs. Pharmacological blockade of prostaglandin E2 biosythesis favors CD103+ dendritic cell activation that primes a Tc1-polarized CD8+ T cell response to bolster tumor rejection. Herein, we postulate that an intricate balance between immunostimulatory and inhibitory DAMPs could determine the outcome of drug-induced ICD and pose COX-2/prostaglandin E2 blockade as a strategy to harness ICD.

MATERIALS
Product Number
Brand
Product Description

Sigma-Aldrich
Doxycycline hyclate
Sigma-Aldrich
Sodium chloride, BioReagent, suitable for cell culture, suitable for insect cell culture, suitable for plant cell culture, ≥99%
Roche
cOmplete, Mini Protease Inhibitor Cocktail, Tablets provided in a glass vial
Millipore
RIPA Lysis Buffer, 10X, 100 mL RIPA Lysis Buffer, 10X for Immunoprecipitation & Western Blotting.
Sigma-Aldrich
RPMI-1640 Medium, With L-glutamine and sodium bicarbonate, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Dulbecco′s Phosphate Buffered Saline, Modified, without calcium chloride and magnesium chloride, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Dulbecco′s Modified Eagle′s Medium - high glucose, With 4500 mg/L glucose, L-glutamine, and sodium bicarbonate, without sodium pyruvate, liquid, sterile-filtered, suitable for cell culture
Sigma-Aldrich
cis-Diammineplatinum(II) dichloride, crystalline
Sigma-Aldrich
Fetal Bovine Serum, USDA approved, sterile-filtered, suitable for cell culture
Sigma-Aldrich
Trizma® hydrochloride solution, pH 7.4, BioPerformance Certified, 1 M, suitable for cell culture
Sigma-Aldrich
Dulbecco′s Modified Eagle′s Medium/Nutrient Mixture F-12 Ham, With 15 mM HEPES and sodium bicarbonate, without L-glutamine, liquid, sterile-filtered, suitable for cell culture