Context Assessment for Agroecology Transformation in the Tunisian Living Landscape

The purpose of this Context Assessment is threefold: first, to characterize the environmental, social and economic and political contexts of the Tunisian ALL; second, to understand the data and information currently available in sub-region of the ALL, and third to characterize the extent to which agroecological principles are already being employed locally at the ALL levels. This report constitutes a basis of information and discussion to conduct the impact assessment. It is also valuable to all WPs in the Initiative as it provides critical quantitative or qualitative data and information regarding capacities assessment, policy influence, and other environmental attributes which can guide the initiative implementation and impact in 2023/2024. The present Context Assessment in Tunisia has been elaborated from primary and secondary sources of data. The primary sources of data are issued from focus groups and formal and informal interviews conducted in the targeted area between June and December 2022, as part of WP1 and WP4 activities. The secondary sources of data came from previous research and development projects, in addition to formal and grey literature or technical reports and policy documents. This report will be enriched with a household survey planned during the first quarter of 2023. This report contributes to Output 2.1. Baseline – current conditions of agricultural systems of small holder farmers in each ALL, Output 1.1 on establishment of the ALL, Output 4.1 on the identification of policies and local institutions and their role in the AE pathways

LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer

Tumor-associated macrophages (TAMs) are a heterogeneous population of cells that facilitate cancer progression. However, our knowledge of the niches of individual TAM subsets and their development and function remain incomplete. Here, we describe a population of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)-expressing TAMs, which form coordinated multi-cellular “nest” structures that are heterogeneously distributed proximal to vasculature in tumors of a spontaneous murine model of breast cancer. We demonstrate that LYVE-1+ TAMs develop in response to IL-6, which induces their expression of the immune-suppressive enzyme heme oxygenase-1 and promotes a CCR5-dependent signaling axis, which guides their nest formation. Blocking the development of LYVE-1+ TAMs or their nest structures, using gene-targeted mice, results in an increase in CD8+ T cell recruitment to the tumor and enhanced response to chemotherapy. This study highlights an unappreciated collaboration of a TAM subset to form a coordinated niche linked to immune exclusion and resistance to anti-cancer therapy

LYVE-1+ macrophages form a collaborative CCR5-dependent perivascular niche that influences chemotherapy responses in murine breast cancer.

Tumor-associated macrophages (TAMs) are a heterogeneous population of cells that facilitate cancer progression. However, our knowledge of the niches of individual TAM subsets and their development and function remain incomplete. Here, we describe a population of lymphatic vessel endothelial hyaluronan receptor-1 (LYVE-1)-expressing TAMs, which form coordinated multi-cellular "nest" structures that are heterogeneously distributed proximal to vasculature in tumors of a spontaneous murine model of breast cancer. We demonstrate that LYVE-1 + TAMs develop in response to IL-6, which induces their expression of the immune-suppressive enzyme heme oxygenase-1 and promotes a CCR5-dependent signaling axis, which guides their nest formation. Blocking the development of LYVE-1 + TAMs or their nest structures, using gene-targeted mice, results in an increase in CD8 + T cell recruitment to the tumor and enhanced response to chemotherapy. This study highlights an unappreciated collaboration of a TAM subset to form a coordinated niche linked to immune exclusion and resistance to anti-cancer therapy

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

Background: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. Methods: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. Findings: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. Interpretation: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic

Global burden and strength of evidence for 88 risk factors in 204 countries and 811 subnational locations, 1990–2021: a systematic analysis for the Global Burden of Disease Study 2021

Background: Understanding the health consequences associated with exposure to risk factors is necessary to inform public health policy and practice. To systematically quantify the contributions of risk factor exposures to specific health outcomes, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 aims to provide comprehensive estimates of exposure levels, relative health risks, and attributable burden of disease for 88 risk factors in 204 countries and territories and 811 subnational locations, from 1990 to 2021. Methods: The GBD 2021 risk factor analysis used data from 54 561 total distinct sources to produce epidemiological estimates for 88 risk factors and their associated health outcomes for a total of 631 risk–outcome pairs. Pairs were included on the basis of data-driven determination of a risk–outcome association. Age-sex-location-year-specific estimates were generated at global, regional, and national levels. Our approach followed the comparative risk assessment framework predicated on a causal web of hierarchically organised, potentially combinative, modifiable risks. Relative risks (RRs) of a given outcome occurring as a function of risk factor exposure were estimated separately for each risk–outcome pair, and summary exposure values (SEVs), representing risk-weighted exposure prevalence, and theoretical minimum risk exposure levels (TMRELs) were estimated for each risk factor. These estimates were used to calculate the population attributable fraction (PAF; ie, the proportional change in health risk that would occur if exposure to a risk factor were reduced to the TMREL). The product of PAFs and disease burden associated with a given outcome, measured in disability-adjusted life-years (DALYs), yielded measures of attributable burden (ie, the proportion of total disease burden attributable to a particular risk factor or combination of risk factors). Adjustments for mediation were applied to account for relationships involving risk factors that act indirectly on outcomes via intermediate risks. Attributable burden estimates were stratified by Socio-demographic Index (SDI) quintile and presented as counts, age-standardised rates, and rankings. To complement estimates of RR and attributable burden, newly developed burden of proof risk function (BPRF) methods were applied to yield supplementary, conservative interpretations of risk–outcome associations based on the consistency of underlying evidence, accounting for unexplained heterogeneity between input data from different studies. Estimates reported represent the mean value across 500 draws from the estimate's distribution, with 95% uncertainty intervals (UIs) calculated as the 2·5th and 97·5th percentile values across the draws. Findings: Among the specific risk factors analysed for this study, particulate matter air pollution was the leading contributor to the global disease burden in 2021, contributing 8·0% (95% UI 6·7–9·4) of total DALYs, followed by high systolic blood pressure (SBP; 7·8% [6·4–9·2]), smoking (5·7% [4·7–6·8]), low birthweight and short gestation (5·6% [4·8–6·3]), and high fasting plasma glucose (FPG; 5·4% [4·8–6·0]). For younger demographics (ie, those aged 0–4 years and 5–14 years), risks such as low birthweight and short gestation and unsafe water, sanitation, and handwashing (WaSH) were among the leading risk factors, while for older age groups, metabolic risks such as high SBP, high body-mass index (BMI), high FPG, and high LDL cholesterol had a greater impact. From 2000 to 2021, there was an observable shift in global health challenges, marked by a decline in the number of all-age DALYs broadly attributable to behavioural risks (decrease of 20·7% [13·9–27·7]) and environmental and occupational risks (decrease of 22·0% [15·5–28·8]), coupled with a 49·4% (42·3–56·9) increase in DALYs attributable to metabolic risks, all reflecting ageing populations and changing lifestyles on a global scale. Age-standardised global DALY rates attributable to high BMI and high FPG rose considerably (15·7% [9·9–21·7] for high BMI and 7·9% [3·3–12·9] for high FPG) over this period, with exposure to these risks increasing annually at rates of 1·8% (1·6–1·9) for high BMI and 1·3% (1·1–1·5) for high FPG. By contrast, the global risk-attributable burden and exposure to many other risk factors declined, notably for risks such as child growth failure and unsafe water source, with age-standardised attributable DALYs decreasing by 71·5% (64·4–78·8) for child growth failure and 66·3% (60·2–72·0) for unsafe water source. We separated risk factors into three groups according to trajectory over time: those with a decreasing attributable burden, due largely to declining risk exposure (eg, diet high in trans-fat and household air pollution) but also to proportionally smaller child and youth populations (eg, child and maternal malnutrition); those for which the burden increased moderately in spite of declining risk exposure, due largely to population ageing (eg, smoking); and those for which the burden increased considerably due to both increasing risk exposure and population ageing (eg, ambient particulate matter air pollution, high BMI, high FPG, and high SBP). Interpretation: Substantial progress has been made in reducing the global disease burden attributable to a range of risk factors, particularly those related to maternal and child health, WaSH, and household air pollution. Maintaining efforts to minimise the impact of these risk factors, especially in low SDI locations, is necessary to sustain progress. Successes in moderating the smoking-related burden by reducing risk exposure highlight the need to advance policies that reduce exposure to other leading risk factors such as ambient particulate matter air pollution and high SBP. Troubling increases in high FPG, high BMI, and other risk factors related to obesity and metabolic syndrome indicate an urgent need to identify and implement interventions

Global age-sex-specific mortality, life expectancy, and population estimates in 204 countries and territories and 811 subnational locations, 1950–2021, and the impact of the COVID-19 pandemic: a comprehensive demographic analysis for the Global Burden of Disease Study 2021

BACKGROUND: Estimates of demographic metrics are crucial to assess levels and trends of population health outcomes. The profound impact of the COVID-19 pandemic on populations worldwide has underscored the need for timely estimates to understand this unprecedented event within the context of long-term population health trends. The Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) 2021 provides new demographic estimates for 204 countries and territories and 811 additional subnational locations from 1950 to 2021, with a particular emphasis on changes in mortality and life expectancy that occurred during the 2020–21 COVID-19 pandemic period. METHODS: 22 223 data sources from vital registration, sample registration, surveys, censuses, and other sources were used to estimate mortality, with a subset of these sources used exclusively to estimate excess mortality due to the COVID-19 pandemic. 2026 data sources were used for population estimation. Additional sources were used to estimate migration; the effects of the HIV epidemic; and demographic discontinuities due to conflicts, famines, natural disasters, and pandemics, which are used as inputs for estimating mortality and population. Spatiotemporal Gaussian process regression (ST-GPR) was used to generate under-5 mortality rates, which synthesised 30 763 location-years of vital registration and sample registration data, 1365 surveys and censuses, and 80 other sources. ST-GPR was also used to estimate adult mortality (between ages 15 and 59 years) based on information from 31 642 location-years of vital registration and sample registration data, 355 surveys and censuses, and 24 other sources. Estimates of child and adult mortality rates were then used to generate life tables with a relational model life table system. For countries with large HIV epidemics, life tables were adjusted using independent estimates of HIV-specific mortality generated via an epidemiological analysis of HIV prevalence surveys, antenatal clinic serosurveillance, and other data sources. Excess mortality due to the COVID-19 pandemic in 2020 and 2021 was determined by subtracting observed all-cause mortality (adjusted for late registration and mortality anomalies) from the mortality expected in the absence of the pandemic. Expected mortality was calculated based on historical trends using an ensemble of models. In location-years where all-cause mortality data were unavailable, we estimated excess mortality rates using a regression model with covariates pertaining to the pandemic. Population size was computed using a Bayesian hierarchical cohort component model. Life expectancy was calculated using age-specific mortality rates and standard demographic methods. Uncertainty intervals (UIs) were calculated for every metric using the 25th and 975th ordered values from a 1000-draw posterior distribution. FINDINGS: Global all-cause mortality followed two distinct patterns over the study period: age-standardised mortality rates declined between 1950 and 2019 (a 62·8% [95% UI 60·5–65·1] decline), and increased during the COVID-19 pandemic period (2020–21; 5·1% [0·9–9·6] increase). In contrast with the overall reverse in mortality trends during the pandemic period, child mortality continued to decline, with 4·66 million (3·98–5·50) global deaths in children younger than 5 years in 2021 compared with 5·21 million (4·50–6·01) in 2019. An estimated 131 million (126–137) people died globally from all causes in 2020 and 2021 combined, of which 15·9 million (14·7–17·2) were due to the COVID-19 pandemic (measured by excess mortality, which includes deaths directly due to SARS-CoV-2 infection and those indirectly due to other social, economic, or behavioural changes associated with the pandemic). Excess mortality rates exceeded 150 deaths per 100 000 population during at least one year of the pandemic in 80 countries and territories, whereas 20 nations had a negative excess mortality rate in 2020 or 2021, indicating that all-cause mortality in these countries was lower during the pandemic than expected based on historical trends. Between 1950 and 2021, global life expectancy at birth increased by 22·7 years (20·8–24·8), from 49·0 years (46·7–51·3) to 71·7 years (70·9–72·5). Global life expectancy at birth declined by 1·6 years (1·0–2·2) between 2019 and 2021, reversing historical trends. An increase in life expectancy was only observed in 32 (15·7%) of 204 countries and territories between 2019 and 2021. The global population reached 7·89 billion (7·67–8·13) people in 2021, by which time 56 of 204 countries and territories had peaked and subsequently populations have declined. The largest proportion of population growth between 2020 and 2021 was in sub-Saharan Africa (39·5% [28·4–52·7]) and south Asia (26·3% [9·0–44·7]). From 2000 to 2021, the ratio of the population aged 65 years and older to the population aged younger than 15 years increased in 188 (92·2%) of 204 nations. INTERPRETATION: Global adult mortality rates markedly increased during the COVID-19 pandemic in 2020 and 2021, reversing past decreasing trends, while child mortality rates continued to decline, albeit more slowly than in earlier years. Although COVID-19 had a substantial impact on many demographic indicators during the first 2 years of the pandemic, overall global health progress over the 72 years evaluated has been profound, with considerable improvements in mortality and life expectancy. Additionally, we observed a deceleration of global population growth since 2017, despite steady or increasing growth in lower-income countries, combined with a continued global shift of population age structures towards older ages. These demographic changes will likely present future challenges to health systems, economies, and societies. The comprehensive demographic estimates reported here will enable researchers, policy makers, health practitioners, and other key stakeholders to better understand and address the profound changes that have occurred in the global health landscape following the first 2 years of the COVID-19 pandemic, and longer-term trends beyond the pandemic. FUNDING: Bill & Melinda Gates Foundation

Genetic analysis of caftaric, chlorogenic and chicoric metabolism in Cichorium intybus L. : qTL and candidate genes mapping

Les polyphénols, dont le pouvoir antioxydant a été largement démontré, font partie du métabolisme secondaire, permettant aux plantes de réagir dans un environnement donné. Pour comprendre le contrôle génétique de la biosynthèse des polyphénols synthétisés dans les feuilles de chicorée, une approche QTL (Quantitative Trait Loci) a été effectuée. Dans un premier temps, le protocole d’extraction miniaturisé mis en place a permis d’identifier l’acide caftarique, chlorogénique et chicorique. Une descendance F1’ de 201 individus (K28xK59) a été phénotypée pour la quantité d’acide caftarique (ACAFT), chlorogénique (ACHLO), chicorique (ACHIC), la somme de ces trois molécules (ATOT), l’activité antiradicalaire (AAR) ainsi que le ratio de la quantité d’acide caftarique et d’acide chlorogénique par rapport à l’ensemble des acides phénols détectés en CLHP, soit PCAFT et PCHLO, respectivement. A partir d’une carte de référence, une carte génétique spécifique a été établie : sur les 9 groupes de liaison, 142 marqueurs moléculaires (SSR, AFLP, SSCP et HRM), dont 16 gènes candidats, ont été cartographiés. Vingt QTL ont alors été détectés : 1 pour ACAFT (R² = 16,4%), 3 pour ACHLO (R² = 50%), 2 pour ACHIC (R² = 13,9%), 4 pour AAR (R² = 31%) et 5 pour PACFT (R² = 44%) et PCHLO (R² = 61%). Parmi eux, 8 QTL co-localisent avec 7 gènes candidats codant des enzymes impliquées dans le métabolisme des phénylpropanoïdes. Les résultats de cette étude nous ont permis de fournir pour la première fois des éléments sur le contrôle génétique des acides phénols majeurs détectés sans les feuilles de chicorée, notamment l’acide chicorique et caftarique qui ne sont accumulés que chez quelques espèces.Secondary metabolism corresponds to a class of compounds allowing plants to survive in their environment. Among these molecules, polyphenols display widely studied antioxidant properties. The aim of this work was to study the genetic control of biosynthesis of polyphenols detected in chicory leaf tissue, using a QTL (Quantitative Trait Loci) analysis approach based on a F1’ progeny. First, a high-throughput protocol was set up and permit us to identify caftaric acid, chlorogenic acid and chicoric acid. In this context, 201 individuals from the F1’ progeny were phenotyped for caftaric, chlorogenic and chicoric acid amounts (respectively ACAFT, ACHLO, ACHIC), the total amount for these three molecules (ATOT), the radical scavenging ability (AAR), the ratio between the caftaric acid or chlorogenic acid and the entire phenolic acids detected (PCAFT and PCHLO, respectively). A specific genetic map was established from a previous map already published. Using SSR, AFLP, SSCP, HRM polymorphism, 142 markers covered the nine linkage groups of this map and among them, 16 candidate genes. Altogether, 20 QTLs were then detected: 1 for ACAFT (R² = 16,4%), 3 for ACHLO (R² = 50%), 2 for ACHIC (R² = 13,9%), 4 for AAR (R² = 31%) et 5 for PACFT (R² = 44%) and PCHLO (R² = 61%). Eight QTLs co-localised with 7 encoding-enzymes genes involved in the phenylpropanoid pathway. This study is the first step toward understanding the genetic control of the main phenolic acids in chicory leaves, particularly caftaric and chicoric acid, only synthesised in few species

Therapeutic antibody to 0-acetylated GD2 ganglioside : novel optimization strategies

Les anticorps thérapeutiques spécifiques d’antigènes tumoraux permettent d’améliorer le pronostic des patients atteints de cancers. Leur utilisation se heurte toutefois à des mécanismes d’échappement tumoraux variés. L’identification de ces mécanismes permet aujourd’hui d’envisager différentes stratégies d’optimisation basée sur l’utilisation d’association thérapeutique. Ces aspects ont été étudié ici dans le cadre du ciblage immunologique du marqueur gangliosidique tumorale GD2 O-acétylé dans le cadre du neuroblastome chez l’enfant et du glioblastome chez l’adulte. Nous montrons que les propriétés proapoptotiques des anticorps du GD2 O-acétylé permettent de sensibiliser les cellules tumorales aux agents de chimiothérapie et ainsi un meilleur contrôle du développement tumoral. Plus particulièrement, ce mécanisme s’applique également aux cellules souches cancéreuses, population cellulaire particulièrement résistante aux agents cytotoxiques qui est impliquée dans les échecs thérapeutiques et les rechutes. Cette association soulève toutefois des incertitudes atour des bénéfices sur le long terme car nous montrons qu’elle induit la surexpression tumorale du point de contrôle phagocytaire CD47 et inhibe l’activité phagocytaire dépendante des anticorps anti- GD2 O-acétylé. Ces mécanismes d’échappement tumoraux peuvent être contrôlé par l’utilisation combiné d’inhibiteur de point de contrôle immunologique. Ensemble, ces travaux montrent l’intérêt d’associer les anticorps thérapeutiques du GD2 O-acétylé à la chimiothérapie et à des inhibiteurs de point de contrôle immunologique. Cet intérêt pourrait conduire à la réalisation d’un essai clinique de phase I de la prise en charge des neuroblastomes.Therapeutic antibodies specific for tumor antigens improve the prognosis of cancer patients. Tumor cells, however, develop various escape mechanisms. The identification of these mechanisms allows different optimization strategies based on therapeutic combinations to achieve long term response in patients with cancer. We studied here some of these aspects in the context neuroblastoma and glioblastoma using O-acetylated GD2- specific monoclonal antibodies. We show that the pro-apoptotic activity of O-acetylated GD2- specific antibodies sensitizes tumor cells to chemotherapeutic agents, allowing thereby a more potent tumor control. Mostly, this mechanism also applies to glioma cancer stem cells, a tumor cell subset particularly resistant to cytotoxic agents which is involved in therapeutic failures and relapses. However, this therapeutic combination might not be able to provide long-term benefits because we show that it further induces the CD47 phagocytic checkpoint in tumor cells. This innate immune checkpoint inhibits the phagocytic activity induced by O-acetylated-specific antibodies against opsonized tumor cells. Yet, this tumor escape mechanism can be controlled by immunological checkpoint inhibitors. Together, we provided the proof of concept of tri-therapy approach to achieve long lasting response in patient with neuroblastoma