Lorenzo Galluzzi

Lorenzo Galluzzi
Weill Cornell Medical College | Cornell · Division of Radiation Oncology

Ph.D.

About

701
Publications
255,522
Reads
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82,659
Citations
Citations since 2017
269 Research Items
54952 Citations
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Introduction
I'm intestered in several aspects of the cell biology, encompassing (i) the molecular mechanisms that underpin regulated cancer cell death, in all its forms, (ii) the adaptive responses whereby cancer cells face adverse microenvironmental conditions and chemotherapeutic challenges, including autophagy; and (iii) the molecular and cellular mechanisms whereby dying cancer cells - at least in selected circumstances - are perceived as immunogenic, eliciting a tumor-specific cognate immune response.
Additional affiliations
November 2016 - present
Paris Descartes, CPSC
Position
  • Professor (Associate)
January 2012 - December 2016
Paris Descartes, CPSC
Position
  • LabEx Manager
September 2008 - December 2011
French Institute of Health and Medical Research
Position
  • PostDoc Position
Education
September 2005 - September 2008
Université Paris-Sud 11
Field of study
  • Molecular Oncology
October 1999 - June 2004
Università degli Studi di Modena e Reggio Emilia
Field of study
  • Medical biotechnology

Publications

Publications (701)
Article
Both aging and cancer are characterized by a series of partially overlapping "hallmarks" that we subject here to a meta-analysis. Several hallmarks of aging (i.e., genomic instability, epigenetic alterations, chronic inflammation, and dysbiosis) are very similar to specific cancer hallmarks and hence constitute common "meta-hallmarks," while other...
Article
Epithelial ovarian carcinoma (EOC) is virtually insensitive to immune checkpoint inhibitors (ICIs). Recent findings from an innovative mouse model of EOC demonstrate that senescence induction underlies the increased sensitivity of homologous recombination-defective EOCs to platinum-based chemotherapy as it initiates tumor infiltration by immune eff...
Article
Full-text available
The anticancer immune response is shaped by immunogenic cell stress and death pathways. Thus, cancer cells can release danger-associated molecular patterns that act on pattern recognition receptors expressed by dendritic cells and their precursors to elicit an antitumor immune response. Here, we investigated the impact of single nucleotide polymorp...
Article
When used according to specific dose/fractionation schedules, focal radiotherapy can elicit a systemic anticancer immune response that limits the growth of distant, non-irradiated tumors. Recent data suggest that, at least in some settings, intratumoral macrophages can be educated by CD47 blockage to promote such an 'abscopal' response independent...
Conference Paper
Background CDK4/6 inhibitors are approved in combination with hormonotherapy as a first-line intervention against advanced/metastatic hormone receptor (HR)⁺ HER2⁻ breast cancer, reflecting their ability to extend progression-free survival (PFS) and overall survival (OS) in this patient population.¹⁻³ Nonetheless, >50% of women with HR⁺ breast cance...
Conference Paper
Background Oncolytic peptides are emerging as attractive candidates for the development of novel anticancer regimens¹, reflecting broad cytolytic activities against a variety of malignant (but not normal) cells and a pronounced potential for immunostimulation.² LTX-315 is a synthetic nonameric cationic peptide derived from bovine lactotransferrin³...
Conference Paper
Background Hormone receptor (HR)⁺ breast cancer is a cold tumor that responds poorly to immune checkpoint blockers targeting PD-11,2, calling for the development of therapeutic strategies that inflame the HR⁺ tumor microenvironment to restore PD-1 sensitivity. OX425 is a second-generation poly(ADP)-ribose polymerase 1 (PARP1)-targeting decoy oligon...
Conference Paper
Background Imvax is developing a novel personalized immunotherapeutic platform combining irradiated patient-derived tumor cells and insulin-like growth factor type-1 receptor antisense oligonucleotide (IMV-001) in biodiffusion chambers (BDC; 0.1-micron pores). The combination product IGV-001 was recently evaluated in a newly diagnosed glioblastoma...
Conference Paper
Background Hormone receptor (HR)⁺breast cancer (BC) is responsible for the majority of BCs and -related deaths in the US.¹ Standard treatment for local disease involves surgery, followed by adjuvant endocrine therapy (ET) ± radiation therapy (RT) and/or chemotherapy (CT), depending on risk for relapse. However, many women receive CT and experience...
Conference Paper
Background PT-112 is a novel platinum-pyrophosphate conjugate¹ under clinical development for cancer therapy.²⁻⁵ Besides mediating cytostatic and cytotoxic effects in numerous human and mouse cancer cells, PT-112 elicits various danger signals that are linked to immunogenic cell death (ICD), such as calreticulin exposure, as well as ATP and HMGB1 s...
Article
Full-text available
Natural killer (NK) cells, which are innate lymphocytes endowed with potent cytotoxic activity, have recently attracted attention as potential anticancer therapeutics. While NK cells mediate encouraging responses in patients with leukemia, the therapeutic effects of NK cell infusion in patients with solid tumors are limited. Preclinical and clinica...
Chapter
Mitophagy is a finely regulated mechanism through which eukaryotic cells selectively dispose of supernumerary, permeabilized or otherwise damaged mitochondria through lysosomal degradation. Dysfunctional mitochondria are prone to release potentially cytotoxic factors including reactive oxygen species (ROS) and caspase activators, such as cytochrome...
Article
Endoplasmic reticulum stress can stimulate calreticulin (CALR) presentation on the cell surface, promoting the phagocytic uptake of stressed cells by myeloid cells. Recent findings from Wattrus et al. demonstrate that zebrafish and mouse embryonic macrophages engulf CALR-exposing nascent hematopoietic stem cells to ensure the selective survival of...
Article
The net effect of type I interferon (IFN-I) signaling on tumor control depends on various factors, including the potential engagement of adaptive anticancer immunity. New findings delineate a targetable epigenetic mechanism by which suboptimal IFN-I signaling promotes tumor progression in the context of cancer stem cell expansion and immunoevasion.
Article
Full-text available
A diet rich in saturated fat and carbohydrates causes low-grade chronic inflammation in several organs, including the liver, ultimately driving nonalcoholic steatohepatitis. In this setting, environment-driven lipotoxicity and glucotoxicity induce liver damage, which promotes dendritic cell activation and generates a major histocompatibility comple...
Chapter
When employed according to specific doses and fractionation schedules, radiation therapy (RT) elicits potent tumor-targeting immune responses that rely on the secretion of type I interferon (IFN) by irradiated cancer cells. Most often, this is initiated by the ability of RT to promote the cytosolic accumulation of double-stranded DNA (dsDNA) molecu...
Article
Numerous mitochondrial constituents and metabolic products can function as damage-associated molecular patterns (DAMPs) and promote inflammation when released into the cytosol or extracellular milieu. Several safeguards are normally in place to prevent mitochondria from eliciting detrimental inflammatory reactions, including the autophagic disposal...
Chapter
It is now clear that radiation therapy (RT) can be delivered in doses and according to fractionation schedules that actively elicit immunostimulatory effects. While such effects are often sufficient to drive potent anticancer immunity culminating with systemic disease eradication, the immunostimulatory activity of RT stands out as a promising combi...
Article
Full-text available
Mutations in the TECPR2 gene are the cause of an ultra-rare neurological disorder characterized by intellectual disability, impaired speech, motor delay, and hypotonia evolving to spasticity, central sleep apnea, and premature death (SPG49 or HSAN9; OMIM: 615031). Little is known about the biological function of TECPR2, and there are currently no a...
Chapter
Radiation therapy (RT) is well known for its capacity to mediate cytostatic and cytotoxic effects on malignant cells, largely reflecting the ability of ionizing radiation to cause direct and indirect damage to macromolecules including DNA and lipids. While low-dose RT generally causes limited cytotoxicity in an acute manner (as it imposes insuffici...
Article
e15060 Background: Poly (ADP-ribose) polymerase (PARP) inhibitors mediate significant anticancer effects against homologous recombination defective (HRD) tumors but have limited efficacy against homologous recombination proficient (HRP) neoplasms. Moreover, HRD tumors often become resistant to PARP inhibitors during treatment, constituting a major...
Article
Purpose: The successful implementation of immune checkpoint inhibitors (ICIs) in the clinical management of various solid tumors has raised considerable expectations for patients with epithelial ovarian carcinoma (EOC). However, EOC is poorly responsive to ICIs due to immunological features including limited tumor mutational burden (TMB) and poor...
Article
Myeloid-derived suppressor cells (MDSC) are a heterogeneous population of pathologically activated, mostly immature, myeloid cells that exert robust immunosuppressive functions. MDSCs expand during oncogenesis and have been linked to accelerated disease progression and resistance to treatment in both preclinical tumor models and patients with cance...
Article
Dietary interventions including alterations in the amount or type of specific macronutrients have been shown to mediate antineoplastic effects in preclinical tumor models, but the underlying mechanisms are only partially understood. In this issue of Cancer Research, Wei and colleagues demonstrate that restoring ketogenesis in the colorectal cancer...
Article
Unscheduled tetraploidy is a metastable state that rapidly evolves into aneuploidy. Recent findings reported by Gemble et al. demonstrate that freshly formed tetraploid cells fail to accumulate the required amounts of DNA replication factors during the first G1 phase after whole-genome duplication (WGD), culminating in genetic instability in the su...
Poster
Full-text available
Immunotherapy is a promising therapeutic intervention for cancer treatment. Activation of the immune system via checkpoint blockade has been shown to produce antitumor responses in patients with both solid and hematological tumors. However, many patients do not respond to checkpoint inhibitors, and additional therapies are needed to treat these pat...
Article
Immune checkpoint inhibitors (ICIs) have revolutionized the clinical management of multiple tumours. However, only a few patients respond to ICIs, which has generated considerable interest in the identification of resistance mechanisms. One such mechanism reflects the ability of various oncogenic pathways, as well as stress response pathways requir...
Article
BAX and BAK are generally considered as fully interchangeable for mitochondrial permeabilization and consequent apoptotic cell death. Garcia-Saez and colleagues have recently documented striking kinetic differences that influence BAX and BAK oligomerization at the mitochondrial surface. These data have important implications for inflammatory respon...
Article
At odds with other solid tumors, epithelial ovarian cancer (EOC) is poorly sensitive to immune checkpoint inhibitors (ICIs), largely reflecting active immunosuppression despite CD8+ T cell infiltration at baseline. Accumulating evidence indicates that both conventional chemotherapeutics and targeted anticancer agents commonly used in the clinical m...
Article
Dying mammalian cells emit numerous signals that interact with the host to dictate the immunological correlates of cellular stress and death. In the absence of reactive antigenic determinants (which is generally the case for healthy cells), such signals may drive inflammation but cannot engage adaptive immunity. Conversely, when cells exhibit suffi...
Article
Full-text available
Radiation therapy (RT) is known for its ability to kill cancer cells in an immunogenic manner. Recent preclinical data demonstrate that targeted alpha-particle therapy shares with RT the capacity to elicit immunostimulatory effects, standing out as a promising strategy to circumvent immune checkpoint inhibitor resistance in immunologically ‘cold’ t...
Chapter
Radiation therapy (RT) is well known for its capacity to mediate cytostatic and cytotoxic effects upon the accumulation of unrepaired damage to macromolecules, notably DNA. The ability of ionizing radiation to prevent malignant cells from replicating and to cause their demise is indeed an integral component of the anticancer activity of RT. Neoplas...
Article
Cancer stem cells (CSCs) are known for their superior tumor-initiating and tumor-repopulating potential, partly reflecting their pronounced ability to evade immune recognition. Liu and colleagues recently identified a new aldehyde dehydrogenase (ALDH)-dependent mechanism whereby triple-negative breast CSCs evade immunosurveillance upon recruitment...
Article
Two recent reports in Nature highlight a novel mechanism of immunoevasion that relies on the SET domain bifurcated histone lysine methyltransferase 1 (SETDB1)-dependent epigenetic suppression of endogenous retroelements in melanoma cells. Because SETDB1 is highly expressed by the stem cell compartment, these findings delineate an innovative strateg...
Article
A variety of targeted anticancer agents have been successfully introduced into clinical practice, largely reflecting their ability to inhibit specific molecular alterations that are required for disease progression. However, not all malignant cells rely on such alterations to survive, proliferate, disseminate and/or evade anticancer immunity, imply...
Article
Full-text available
Introduction: Immunotherapy is a promising therapeutic intervention for cancer treatment. Activation of the immune system via checkpoint blockade has been shown to produce antitumor responses in patients with both solid and hematological tumors. However, many patients do not respond to checkpoint inhibitors, and additional therapies are needed to t...
Article
Background Hormone receptor (HR)+ breast cancer (BC) causes most BC-related deaths in the US. ¹ Standard treatment for non-metastatic disease involves surgery plus adjuvant hormonotherapy. However, approximately 50% of patients ultimately relapse and require additional lines of treatment including chemotherapy, which is unfortunately associated wit...
Article
Background Hormone receptor+ (HR+) breast cancer (BC) is the most frequent cause of BC-related deaths. CDK4/6 inhibitors (CDK4/6i) combined with endocrine therapy (ET) emerged as an effective approach for metastatic HR+ BC. However, >60% women with HR+ BC receiving CDK4/6i+ET ultimately relapse, potentially due to activation of poorly characterized...
Article
Background Oncolytic peptides are attractive tools for the development of novel anticancer regimens [1]. LTX-315 is a synthetic peptide with a marked capacity to elicit tumor-targeting immunity in preclinical cancer models [2]. Indeed, LTX-315 has been shown to elicit immunogenic cell death (ICD) in malignant cells [3, 4] and to deplete immunosuppr...
Article
Depending on intensity and duration, STING1 (stimulator of interferon response cGAMP interactor 1) signaling can restrain or promote tumor progression via both cancer cell-intrinsic and -extrinsic pathways. Bruand et al. recently identified a novel STING1-driven immunosuppressive pathway that can be targeted toward superior disease control in precl...
Article
Full-text available
Epithelial ovarian carcinoma (EOC) is a relatively rare malignancy but is the fifth-leading cause of cancer-related death in women, largely reflecting early, prediagnosis dissemination of malignant disease to the peritoneum. At odds with other neoplasms, EOC is virtually insensitive to immune checkpoint inhibitors, correlating with a tumor microenv...
Article
Full-text available
While chemotherapy and radiotherapy remain the first-line approaches for the management of most unresectable tumors, immunotherapy has emerged in the past two decades as a game-changing treatment, notably with the clinical success of immune checkpoint inhibitors. Immunotherapies aim at (re)activating anticancer immune responses which occur in two m...
Article
Mitochondria control various processes that are integral to cellular and organismal homeostasis, including Ca²⁺ fluxes, bioenergetic metabolism, and cell death. Perhaps not surprisingly, multiple pathogenic bacteria have evolved strategies to subvert mitochondrial functions in support of their survival and dissemination. Here, we discuss nonimmunol...
Article
Full-text available
Autophagy is a core molecular pathway for the preservation of cellular and organismal homeostasis. Pharmacological and genetic interventions impairing autophagy responses promote or aggravate disease in a plethora of experimental models. Consistently, mutations in autophagy-related processes cause severe human pathologies. Here, we review and discu...
Article
Full-text available
LTX-315 is a nonameric oncolytic peptide in early clinical development for the treatment of solid malignancies. Preclinical and clinical evidence indicates that the anticancer properties of LTX-315 originate not only from its ability to selectively kill cancer cells, but also from its capacity to promote tumor-targeting immune responses. Here, we i...
Article
Full-text available
Objective DCVAC/OvCa is an active cellular immunotherapy designed to stimulate an immune response against ovarian cancer. We explored the safety and efficacy of DCVAC/OvCa plus carboplatin and gemcitabine in platinum-sensitive ovarian cancer. Methods In this open-label, parallel-group, phase 2 trial (ClinicalTrials.gov number NCT02107950), patient...
Article
Several recent preclinical studies have demonstrated that simultaneously blocking exogenous and endogenous sources of serine in malignant cells mediates superior anticancer effects as compared with limiting either source alone. Here, we critically summarize key developments in targeting serine to treat cancer and discuss persisting challenges for i...
Article
Full-text available
Patients with breast cancer obtain limited clinical benefits from immune checkpoint inhibitors (ICIs), pointing to the existence of multiple immunological alterations that cannot be simultaneously normalized with immunotherapy. Accumulating preclinical evidence suggests that radiation therapy (RT) can be harnessed to sensitize primary and metastati...
Article
While intracellular adenosine triphosphate (ATP) occupies a key position in the bioenergetic metabolism of all the cellular compartments that form the tumor microenvironment (TME), extracellular ATP operates as a potent signal transducer. The net effects of purinergic signaling on the biology of the TME depend not only on the specific receptors and...
Article
Full-text available
Here, we describe an immunofluorescence (IF) microscopy-based approach to quantify cytosolic double-stranded DNA molecules in cultured eukaryotic cells upon the selective and specific permeabilization of plasma membranes. This technique is compatible with widefield microscopy coupled with automated image analysis for mid- to high-throughput applica...
Article
Full-text available
Over the last two decades, a large volume of studies has established that dying and dead cancer cells exert a potent immunomodulatory effect on their immediate microenvironment, which has a major influence on the anticancer immunity. Considerable effort has been devoted to understanding the molecular and cellular mechanisms through which the innate...
Conference Paper
Background. Hormone receptor (HR)+ breast cancer (BC) causes the majority of BC-related deaths in the US (Siegel, Miller et al. 2020). Standard treatment includes surgery, endocrine therapy +/- chemotherapy or radiation therapy (RT), depending on surgical procedure and risk assessment). However, approximately 50% of patients with HR+ do not experie...
Article
Full-text available
Preclinical models of ischemia/reperfusion injury (RI) demonstrate the deleterious effects of permeability transition pore complex (PTPC) opening in the first minutes upon revascularization of the occluded vessel. The ATP synthase c subunit (Csub) influences PTPC activity in cells, thus impacting tissue injury. A conserved glycine-rich domain in Cs...
Article
Hyperglycemia and hyperlipidemia are often observed in individuals with type II diabetes (T2D) and related mouse models. One dysmetabolic biochemical consequence is the non-enzymatic reaction between sugars, lipids, and proteins, favoring protein glycation, glycoxidation, and lipoxidation. Here, we identified oxidative alterations in key components...
Article
Full-text available
Accumulating evidence indicates that immune checkpoint inhibitors (ICIs) can restore CD8⁺ cytotoxic T lymphocyte (CTL) functions in preclinical models of acute myeloid leukemia (AML). However, ICIs targeting programmed cell death 1 (PDCD1, best known as PD-1) and cytotoxic T lymphocyte-associated protein 4 (CTLA4) have limited clinical efficacy in...
Article
Immune checkpoint inhibitors (ICIs) have transformed the treatment of various cancers, including malignancies once considered untreatable. These agents, however, are associated with inflammation and tissue damage in multiple organs. Myocarditis has emerged as a serious ICI-associated toxicity, because, while seemingly infrequent, it is often fulmin...
Article
Full-text available
Radiation therapy (RT) and cyclin-dependent kinase 4/6 (CDK4/6) inhibitors mediate poorly overlapping cytostatic and immunostimulatory effects, suggesting that combinatorial regimens may enable supra-additive tumor control. Our preclinical findings demonstrate that administration schedule stands out as a major determinant of efficacy when RT and CD...
Article
Most (if not all) tumors emerge and progress under a strong evolutionary pressure imposed by trophic, metabolic, immunological, and therapeutic factors. The relative impact of these factors on tumor evolution changes over space and time, ultimately favoring the establishment of a neoplastic microenvironment that exhibits considerable genetic, pheno...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Preprint
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Autophagy is quintessential for the maintenance of cellular homeostasis in all eukaryotic cells, explaining why both normal and malignant cells benefit from proficient autophagic responses. Moreover, autophagy is intimately involved in the immunological control of malignant transformation, tumor progression and response to therapy. However, the net...
Article
Full-text available
With a rising incidence of COVID-19–associated morbidity and mortality worldwide, it is critical to elucidate the innate and adaptive immune responses that drive disease severity. We performed longitudinal immune profiling of peripheral blood mononuclear cells from 45 patients and healthy donors. We observed a dynamic immune landscape of innate and...
Article
Full-text available
Serine is a nonessential amino acid generated by the sequential actions of phosphoglycerate dehydrogenase (PHGDH), phosphoserine aminotransferase (PSAT1), and phosphoserine phosphatase (PSPH). Increased serine biosynthesis occurs in several cancers and supports tumor growth. In addition, cancer cells can harness exogenous serine to enhance their me...
Article
Autologous T cells engineered to express a chimeric antigen receptor (CAR) remain poorly effective against solid tumors, partly because solid neoplasms can establish an immunosuppressive microenvironment. Recent findings by Srivastava et al. suggest that immunogenic chemotherapeutics such as oxaliplatin can be harnessed to maximize the capacity of...
Article
Purpose: Recent preclinical data suggest that cyclin-dependent kinase 4/6 (CDK4/6) inhibition may be harnessed to sensitize estrogen receptor (ER)+ breast cancer (BC) to radiation therapy (RT). However, these findings were obtained in human ER+ BC cell lines exposed to subclinical doses of CDK4/6 inhibitors with limited attention to treatment sche...
Article
Neoantigens generated by somatic non-synonymous mutations are key targets of tumor-specific T cells, but only a small number of mutations predicted to be immunogenic are presented by MHC molecules on cancer cells. Vaccination studies in mice and patients have shown that the majority of neoepitopes that elicit T cell responses fail to induce signifi...
Article
Carbohydrate-rich diets have been consistently associated with detrimental effects for human health, including diabetes and obesity. Moreover, high glucose levels appear to mediate immunosuppressive effects in preclinical tumor models. Recent data from Ferrere and colleagues point to the intriguing possibility that carbotoxicity may originate from...
Article
Accumulating preclinical and clinical evidence indicates that high degrees of heterogeneity among malignant cells constitute a considerable obstacle to the success of cancer therapy. This calls for the development of approaches that operate – or enable established treatments to operate – despite such intratumoral heterogeneity (ITH). In this contex...
Preprint
Full-text available
the PDF can be download freely on pubmed. https://pubmed.ncbi.nlm.nih.gov/33634751/
Cover Page
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...
Article
Full-text available
In 2008, we published the first set of guidelines for standardizing research in autophagy. Since then, this topic has received increasing attention, and many scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Thus, it is important to formulate on a regular basis updated guidelines for monit...