scholarly journals Abstract 3734: Cancer cell-targeted photoimmunotherapy elicits immunogenic cell death and activates the innate and adaptive immune response in the tumor microenvironment

2019 ◽  
Author(s):  
Michelle A. Hsu ◽  
Stephanie M. Okamura ◽  
Daniele M. Bergeron ◽  
Deepak Yadav ◽  
Jerry J. Fong ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Tumor Microenvironment ◽  
Cancer Cell ◽  
Adaptive Immune Response ◽  
Immunogenic Cell Death ◽  
Adaptive Immune

scholarly journals Consensus guidelines for the definition, detection and interpretation of immunogenic cell death

2020 ◽  
Vol 8 (1) ◽  
pp. e000337 ◽  
Author(s):  
Lorenzo Galluzzi ◽  
Ilio Vitale ◽  
Sarah Warren ◽  
Sandy Adjemian ◽  
Patrizia Agostinis ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Adaptive Immune Response ◽  
Operational Definition ◽  
Immunogenic Cell Death ◽  
Adaptive Immune ◽  
Regulated Cell Death ◽  
Definition Of

Cells succumbing to stress via regulated cell death (RCD) can initiate an adaptive immune response associated with immunological memory, provided they display sufficient antigenicity and adjuvanticity. Moreover, multiple intracellular and microenvironmental features determine the propensity of RCD to drive adaptive immunity. Here, we provide an updated operational definition of immunogenic cell death (ICD), discuss the key factors that dictate the ability of dying cells to drive an adaptive immune response, summarize experimental assays that are currently available for the assessment of ICD in vitro and in vivo, and formulate guidelines for their interpretation.

Rediscovery of Nanoparticle-based Therapeutics: Boosting Immunogenic Cell Death for Potential Application in Cancer Immunotherapy

2021 ◽  
Author(s):  
Suah Yang ◽  
In-Cheol Sun ◽  
Hee Sook Hwang ◽  
Man Kyu Shim ◽  
Hong Yeol Yoon ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Cancer Immunotherapy ◽  
Potential Application ◽  
Adaptive Immune Response ◽  
Immunogenic Cell Death ◽  
Living Body ◽  
Adaptive Immune ◽  
Physical Stimuli ◽  
Molecular Patterns

Immunogenic cell death (ICD) occurred by chemical and physical stimuli has shown the potential to activate an adaptive immune response in the immune-competent living body through releasing danger-associated molecular patterns...

scholarly journals Nano-Pulse Stimulation induces immunogenic cell death in human papillomavirus-transformed tumors and initiates an adaptive immune response

PLoS ONE ◽  
2018 ◽  
Vol 13 (1) ◽  
pp. e0191311 ◽  
Author(s):  
Joseph G. Skeate ◽  
Diane M. Da Silva ◽  
Elena Chavez-Juan ◽  
Snjezana Anand ◽  
Richard Nuccitelli ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Human Papillomavirus ◽  
Adaptive Immune Response ◽  
Immunogenic Cell Death ◽  
Adaptive Immune ◽  
Pulse Stimulation

Identification of a Novel Toll-Like Receptor-Independent Immunoadjuvant Pathway That Depends upon Programmed Cell Death.

Blood ◽  
2004 ◽  
Vol 104 (11) ◽  
pp. 775-775
Author(s):  
Kasper Hoebe ◽  
Edith Janssen ◽  
Bruce Beutler
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Immune Responses ◽  
Ultraviolet Light ◽  
Adaptive Immune Response ◽  
Type I ◽  
Toll Like Receptors ◽  
Adjuvant Effect ◽  
Tlr Signaling ◽  
Adaptive Immune

Abstract Molecules of microbial origin, and synthetic derivatives of these molecules, have long been used for their immuno-adjuvant effect, and as the key sensors of microbial infection, Toll-like receptors (TLRs) are thought to be essential for adjuvanticity. To the contrary, we now demonstrate the existence of a robust, TLR-independent pathway for adjuvant effect: one that is actually far stronger than the TLR-dependent pathway. Activation of Toll-like receptors (TLRs) and the subsequent production of cytokines such as type I interferon leads to the maturation of dendritic cells (DCs) with upregulation of MHC molecules and costimulatory molecules such as CD40, CD80 and CD86, allowing for optimal interaction between DCs and T-cells. We have determined that TLR signal transduction is minimally dependent upon two adapter proteins, MyD88 and TRIF. In compound homozygous mutant (DKO) mice that lack functional MyD88 and TRIF, there is complete abrogation of all TLR signaling. Such animals therefore comprise a unique model with which to study TLR-independent immune responses. We have now used DKO mice to determine whether an adaptive immune response can be obtained in the absence of TLR signaling. As expected, adjuvanticity obtained via “classical” microbial adjuvants such as complete Freund’s adjuvant or LPS was completely absent in DKO mice. However, subcutaneous administration of syngeneic murine cells expressing ovalbumin and rendered apoptotic by exposure to ultraviolet light resulted in a strong T-cell response in vivo, with impressive production of interferon-g by CD8+ cells and efficient killing of EL-4 cells that expressed CD8-specific OVA peptides, both in wildtype and DKO mice. Adjuvanticity was observed only in the context of apoptosis, in that living cells, not exposed to ultraviolet light before injection, induced little or no response. Moreover, the mixture of the protein antigen with apoptotic cells was insufficient to induce an adaptive immune response; rather, only cells that expressed the protein prior to induction of apoptosis were stimulatory. These results indicate the existence of a specific, cell death-dependent mechanism for adjuvanticity that is TLR-independent and induced by endogenous molecules. We propose that this new adjuvant pathway is of fundamental importance to immune responses at large. We believe that it is required for initiation of the adaptive immune response witnessed in the context of allograft rejection, graft-versus-host disease, and autoimmune diseases as well.

scholarly journals Cancer cell CCR2 orchestrates suppression of the adaptive immune response

2020 ◽  
Vol 217 (10) ◽  
Author(s):  
Miriam R. Fein ◽  
Xue-Yan He ◽  
Ana S. Almeida ◽  
Emilis Bružas ◽  
Arnaud Pommier ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Immune Response ◽  
Cancer Cells ◽  
Cancer Cell ◽  
Breast Cancer Cells ◽  
Adaptive Immune Response ◽  
Adaptive Immune ◽  
Genetic Targeting ◽  
Dc Maturation

C-C chemokine receptor type 2 (CCR2) is expressed on monocytes and facilitates their recruitment to tumors. Though breast cancer cells also express CCR2, its functions in these cells are unclear. We found that Ccr2 deletion in cancer cells led to reduced tumor growth and approximately twofold longer survival in an orthotopic, isograft breast cancer mouse model. Deletion of Ccr2 in cancer cells resulted in multiple alterations associated with better immune control: increased infiltration and activation of cytotoxic T lymphocytes (CTLs) and CD103+ cross-presenting dendritic cells (DCs), as well as up-regulation of MHC class I and down-regulation of checkpoint regulator PD-L1 on the cancer cells. Pharmacological or genetic targeting of CCR2 increased cancer cell sensitivity to CTLs and enabled the cancer cells to induce DC maturation toward the CD103+ subtype. Consistently, Ccr2−/− cancer cells did not induce immune suppression in Batf3−/− mice lacking CD103+ DCs. Our results establish that CCR2 signaling in cancer cells can orchestrate suppression of the immune response.

scholarly journals 618 Vedotin ADCs induce ER stress and elicit hallmarks of ICD across multiple cancer indications

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A654-A654
Author(s):  
Kerry Klussman ◽  
Elena-Marie Tenn ◽  
Shaylin Higgins ◽  
Rebecca Mazahreh ◽  
Katie Snead ◽  
...  
Keyword(s):  
Immune Response ◽  
Cell Death ◽  
Stress Response ◽  
Cell Surface ◽  
Er Stress ◽  
Immune Cell ◽  
Adaptive Immune Response ◽  
Cytotoxic Agents ◽  
Er Stress Response ◽  
Adaptive Immune

BackgroundEffective cancer treatment requires durable elimination of malignant cells. Cytotoxic chemotherapeutic agents used to treat cancer often show initial anti-tumor efficacy, but fail to produce long-term durable responses in patients. The elicitation of durable responses and improved survival in response to cytotoxic agents may be associated with the induction of innate and adaptive immune response to the cancer. For example, tumor cells undergoing apoptosis following exposure to some cytotoxic agents emit immunostimulatory damage-associated molecular patterns (DAMPs), this form of cell death is termed immunogenic cell death (ICD). ICD can promote the recruitment and activation of both the innate and adaptive immune system, providing an additional mechanism to drive an anti-tumor response.MethodsVedotin-based antibody drug conjugates (ADCs) drive cytotoxicity in tumor cells by engaging tumor antigens on the cell surface, internalizing with the cell surface antigen, and delivering monomethyl auristatin E (MMAE) payload. Following intracellular delivery, MMAE induces mitotic arrest, as well as an endoplasmic reticulum (ER) stress response resulting from microtubule disruption. Following tumor cell treatment, indicators of the ER stress response are observed with vedotin-based ADCs including induction of phospho-JNK and CHOP, This mechanism of MMAE induced ER stress results in emission of hallmark ICD DAMPs including cell-surface calreticulin, extracellular release of HMGB1 and ATP. In this presentation we highlight the ability of MMAE to induce the hallmarks of ICD in multiple cancers across different tissue origins using distinct valine-citrulline-MMAE (vedotin)-based ADCs.ResultsThe culmination of these ICD hallmarks resulted in innate immune cell activation in vitro and in vivo in mouse xenograft models. Tumor bearing mice treated with vedotin-based ADCs resulted in the promotion of immune cell recruitment and activation in tumors. Analysis of immune activation by vedotin-based ADCs included production of innate cytokines and upregulation of HLA/MHC-Class I/II expression, which supports a role in activating both the innate and adaptive immune response. To further our understanding of the potent and broad ability of vedotin ADCs to induce ICD, we have also begun to examine the ICD potential of different classes of ADC payloads including other microtubule inhibitors (auristatins and maytansines), and DNA damaging agents (DNA alkylators or topoisomerase inhibitors). Initial data indicate differences in ICD induction by these agents.ConclusionsThese results help build the rationale for vedotin-based ADCs as preferred partners for immune checkpoint blockade agents.Ethics ApprovalStudies with human samples were performed according to institutional ethics standards. Animal studies were approved by and conducted in accordance with Seattle Genetics Institutional Care and Use Committee protocol #SGE-029.

scholarly journals Colon cancer cell treatment with rose bengal generates a protective immune response via immunogenic cell death

2017 ◽  
Vol 8 (2) ◽  
pp. e2584-e2584 ◽  
Author(s):  
Jianzhong Qin ◽  
Nicholas Kunda ◽  
Guilin Qiao ◽  
Jed F Calata ◽  
Krunal Pardiwala ◽  
...  
Keyword(s):  
Colon Cancer ◽  
Immune Response ◽  
Cell Death ◽  
Cancer Cell ◽  
Rose Bengal ◽  
Colon Cancer Cell ◽  
Protective Immune Response ◽  
Immunogenic Cell Death

scholarly journals Cancer cell CCR2 orchestrates suppression of the adaptive immune response

immuneACCESS ◽  
2020 ◽  
Author(s):  
MR Fein ◽  
X He ◽  
AS Almeida ◽  
E Bruzas ◽  
A Pommier ◽  
...  
Keyword(s):  
Immune Response ◽  
Cancer Cell ◽  
Adaptive Immune Response ◽  
Adaptive Immune
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