Do Mathematics and Reading Skills Impact Student Science Outcomes?

Establishing validated science programs for students with or at risk for learning disabilities requires testing treatment effects and exploring differential response patterns. This study explored whether students' initial mathematics and reading skills influenced their treatment response to a whole-class, second-grade science program called Scientific Explorers (Sci2). The original Sci2 study employed a cluster randomized controlled design and included 294 students from 18 second-grade classrooms. Differential effects of the program by initial mathematics and reading skill levels were not observed for an interactive science assessment and a distal science outcome measure. However, based on initial reading skill levels, moderation results were found on a science vocabulary measure, suggesting the effects of Sci2 were greatest for students with higher initial reading skills. Similar results were found using initial mathematics skill levels as a predictor of differential response such that students with higher mathematics skills reaped stronger treatment effects on the vocabulary measure. Further, we found initial mathematics skills also influenced outcomes on the proximal science content assessment, where students with higher initial mathematics skills led to higher outcomes. Overall, findings suggest Sci2 produced robust effects for all students (g = 0.24-1.23), regardless of initial skill proficiencies. Implications for exploring differential response in science intervention research are discussed.

Exploration of differential responses to FODMAPs and gluten in people with irritable bowel syndrome- a double-blind randomized cross-over challenge study.

INTRODUCTION: There is large variation in response to diet in irritable bowel syndrome (IBS) and determinants for differential response are poorly understood. OBJECTIVES: Our aim was to investigate differential clinical and molecular responses to provocation with fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) and gluten in individuals with IBS. METHODS: Data were used from a crossover study with week-long interventions with either FODMAPs, gluten or placebo. The study also included a rapid provocation test. Molecular data consisted of fecal microbiota, short chain fatty acids, and untargeted plasma metabolomics. IBS symptoms were evaluated with the IBS severity scoring system. IBS symptoms were modelled against molecular and baseline questionnaire data, using Random Forest (RF; regression and clustering), Parallel Factor Analysis (PARAFAC), and univariate methods. RESULTS: Regression and classification RF models were in general of low predictive power (Q2 ≤ 0.22, classification rate < 0.73). Out of 864 clustering models, only 2 had significant associations to clusters (0.69 < CR < 0.73, p < 0.05), but with no associations to baseline clinical measures. Similarly, PARAFAC revealed no clear association between metabolome data and IBS symptoms. CONCLUSION: Differential IBS responses to FODMAPs or gluten exposures could not be explained from clinical and molecular data despite extensive exploration with different data analytical approaches. The trial is registered at www. CLINICALTRIALS: gov as NCT03653689 31/08/2018.

Different immune contextures underlie tumor site-specific responses to immune checkpoint blockade in esophageal cancer.

Immune checkpoint inhibitors (ICIs) have demonstrated efficacy in advanced esophageal squamous cell carcinoma (ESCC). Heterogeneous responses to ICIs have been reported previously. Here, we describe a patient with advanced ESCC exhibiting a response to durvalumab plus tremelimumab for more than 6 months except primary resistant esophageal tumor. The esophageal tumor had higher regulatory T cells, neutrophils, and mast cells scores estimated by NanoString platform than hepatic tumor. The immunohistochemistry study confirmed higher expression levels of Foxp3, and myeloperoxidase (MPO) in the esophageal tumor. The different immune contextures may underlie the heterogeneous responses to ICI combination in this ESCC patient.

Environmental factors regulate soil microbial attributes and their response to drought in rangeland ecosystems.

In ecosystems, soil microbial variables characterization are used to determine soil biological health and the response of soils to environmental stress. Although there are strong associations between plants and soil microorganisms, they may respond asynchronously to environmental factors and severe droughts. We aimed to: I) evaluate the special variation of soil microbiome such as microbial biomass carbon (MBC) and nitrogen (MBN), soil basal respiration (SBR) and microbial indexes in eight rangeland sites located across an aridity gradient (distributed from arid to mesic climates); II) analyze the relative importance of main environmental factors (climate, soils, and plants) and their relationships with microbial variables in the rangelands; and III) assess the effect of drought on microbial and plant variables in field-based manipulative experiments. First, we found significant changes of microbial variables along a precipitation and temperature gradient. The responses of MBC and MBN were strongly dependent on soil pH, soil nitrogen (N), soil organic carbon (SOC), C:N ratio and vegetation cover. In contrast, SBR was influenced by the aridity index (AI), the mean annual precipitation (MAP), the soil pH and vegetation cover. MBC, MBN and SBR were negatively related with soil pH compared to the other factors (C, N, C:N, vegetation cover, MAP and AI) that had a positive relationship. Second, we found a stronger soil microbial variables response to drought in arid sites compared to humid rangelands. Third, the responses of MBC, MBN, and SBR to drought showed positive relationships with vegetation cover and aboveground biomass, but with different regression slopes, this suggest that plant and microbial communities responded differently to drought. The results from this study improve our understanding about the microbial response to drought in different rangelands, and may facilitate the development of predictive models on responses of soil microorganisms in carbon cycle under global change scenarios.

Apelin as a Potential Regulator of Peak Athletic Performance.

Apelin, as a cardiokine/myokine, is emerging as an important regulator of cardiac and skeletal muscle homeostasis. Loss of apelin signaling results in premature cardiac aging and sarcopenia. However, the contribution of apelin to peak athletic performance remains largely elusive. In this paper, we assessed the impact of maximal cardiorespiratory exercise testing on the plasma apelin levels of 58 male professional soccer players. Circulating apelin-13 and apelin-36, on average, increased transiently after a single bout of treadmill exercise; however, apelin responses (Δapelin = peak - baseline values) showed a striking interindividual variability. Baseline apelin-13 levels were inversely correlated with those of Δapelin-13 and Δapelin-36. Δapelin-13 showed a positive correlation with the maximal metabolic equivalent, relative maximal O2 consumption, and peak circulatory power, whereas such an association in the case of Δapelin-36 could not be detected. In conclusion, we observed a pronounced individual-to-individual variation in exercise-induced changes in the plasma levels of apelin-13 and apelin-36. Since changes in plasma apelin-13 levels correlated with the indicators of physical performance, whole-body oxygen consumption and pumping capability of the heart, apelin, as a novel exerkine, may be a determinant of peak athletic performance.

The more we change the more we stay the same: Canadian child welfare systems' response to child well-being.

BACKGROUND: Child welfare services in Canada are guided by a dual mandate: to protect children from imminent harm and to promote their optimal development and well-being. To understand how child welfare systems respond to this dual mandate, Trocmé et al. (2014) developed a taxonomy to classify child welfare investigations as either being related to urgent protection or chronic needs. OBJECTIVE: To extend Trocmé et al.'s (2014) analysis using data from the Canadian Incidence Study of Reported Child Abuse and Neglect 2019 (CIS-2019). PARTICIPANTS AND SETTING: The CIS-2019 employs a file review methodology to collect information on child maltreatment-related investigations conducted in Canada in 2019. The study's unweighted sample included 41,948 investigations involving children aged 0-15 years. METHODS: Secondary analyses of the CIS-2019 were conducted including frequency counts and bivariate analyses. RESULTS: Ninety percent of investigations conducted in Canada in 2019 were focused on concerns related to chronic needs. Most investigations (90.9 % of urgent protection investigations and 98.3 % of chronic needs investigations) did not involve physical harm to the child. Urgent protection investigations were less likely to have been previously investigated and more likely to be substantiated, involve a child welfare court application, or involve a placement in out-of-home care. CONCLUSIONS: Most child welfare investigations in Canada continue to be focused on chronic needs. Yet, the investigation response seems designed to respond to urgent protection concerns. A truly differential model is needed to appropriately respond to the dual mandate of Canadian child welfare services and better serve children and families.

Differential Response and the Reduction of Child Maltreatment and Foster Care Services Utilization in the U.S. From 2004 to 2017.

By 2014, the majority of U.S. states had implemented differential response (DR), a system policy that seeks to serve families of low-to moderate-risk for child maltreatment through family engagement, diversion from formal child protective services investigations, and service provision. However, the effects of DR programs on child welfare dynamics have yet to be evaluated nationally using causal methods. Using a quasi-experimental study design with data drawn from the National Child Abuse and Neglect Data System from 2004 to 2017, we found states with DR programs had approximately 19% fewer substantiated reports, 25% fewer children substantiated for neglect, and a 17% reduction in foster care services utilization when compared to states without DR programs. We find these estimates to be robust to the opioid epidemic and incarceration rates. Additional research is needed to better characterize DR programs and isolate the effects of DR programs geographically.

Brief Report: Machine Learning for Estimating Prognosis of Children with Autism Receiving Early Behavioral Intervention-A Proof of Concept.

Although early behavioral intervention is considered as empirically-supported for children with autism, estimating treatment prognosis is a challenge for practitioners. One potential solution is to use machine learning to guide the prediction of the response to intervention. Thus, our study compared five machine algorithms in estimating treatment prognosis on two outcomes (i.e., adaptive functioning and autistic symptoms) in children with autism receiving early behavioral intervention in a community setting. Each machine learning algorithm produced better predictions than random sampling on both outcomes. Those results indicate that machine learning is a promising approach to estimating prognosis in children with autism, but studies comparing these predictions with those produced by qualified practitioners remain necessary.

A Review of Screened-Out Families and Child Protective Services Involvement: A Missed Opportunity to Prevent Future Maltreatment With Community-Based Services.

The objective of this article is to frame, understand, and draw implications from existing research on families screened out by child protective services (CPS) after a referral alleging child maltreatment. We review descriptive and outcome data together with emerging intervention research amidst a developing consensus that the current reactive role of CPS should be supplemented by supportive and preventative services that primarily address poverty. State-level data indicate that screened-out families are at high risk of re-referral and similar to higher-risk families reported to CPS. Intervention research is scant and mixed, but there is indication that providing community-based services may reduce future CPS involvement. Considering that screened-out referrals present an opportunity to prevent future maltreatment, CPS should identify and collaboratively engage screened-out families in community-based services. More research on the outcomes of these community responses is needed to identify best practices related to engagement and service provision.

Major findings from the Ontario Incidence Study of Reported Child Abuse and Neglect 2018.

BACKGROUND: The Ontario Incidence Study of Reported Child Abuse and Neglect (OIS) is the only source of province-wide statistics on families investigated by child welfare. OBJECTIVE: This paper presents key findings from the 2018 cycle of the OIS (OIS-2018) and highlights select policy and practice implications of these findings. PARTICIPANTS AND SETTINGS: The OIS-2018 captured information directly from investigating child protection workers about children and families who were the subject of a child protection investigation sampled for inclusion in the study. METHODS: The OIS-2018 sample was drawn in three stages: first, a representative sample of child welfare agencies in Ontario was selected, then cases were sampled over a three-month period within selected agencies, and, finally, investigations that met the study criteria were identified from the sampled cases. The data collected for the OIS-2018 were weighted in order to derive provincial, annual incidence estimates. RESULTS: An estimated 158,476 child maltreatment-related investigations were conducted in Ontario in 2018. In the majority of investigations, there was no documented physical or emotional harm to the child. The overall incidence of investigations remains unchanged between 2008 and 2018. The only statistically significant difference during this time period is an increase in risk investigations between 2013 and 2018. CONCLUSIONS: Data from the OIS gives Ontario child welfare policymakers and practitioners an empirical basis for making evidence-informed decisions. Findings are compared to the United States and Australia.

Accessing Alternative Response Payways: A Multi-Level Examination of Family and Community Factors on Race Equity.

BACKGROUND: Although research has identified factors associated with child welfare involvement, less attention has been paid to how Black families are assigned to types of child welfare responses. The advent of alternative response pathways allows child protection workers to assign child abuse and neglect responses to families based on the type and seriousness of the maltreatment, history of prior reports and age of the child. OBJECTIVE: The effects of family and community characteristics on alternative response pathways are examined by exploring decision-making at two points in the child welfare system: access to an alternative response child welfare system and assignment to either an investigative or alternative response pathway. PARTICIPANTS AND SETTING: Black and White families reported for child abuse and neglect (N = 31,802) in New York State were studied. METHODS: Using data from the National Child Abuse and Neglect Data System matched with New York State county socioeconomic indicators, logistic and multi-level analyses examined the effect of county-level variables on family characteristics. RESULTS: The analysis determined that Black children and families were not assigned to alternative response pathways similarly to White families especially in counties where indication rates were higher. CONCLUSION: Findings imply that Black families involved in the child welfare system may benefit from increased access to culturally responsive interventions that target neighborhoods with high indication rates.

Dietary RNAi toxicity assay exhibits differential responses to ingested dsRNAs among lady beetles.

BACKGROUND: Most recently, major federal regulatory agencies deregulated an in planta RNA interference (RNAi) trait against a devastating corn pest, the western corn rootworm Diabrotica virgifera virgifera, in the United States and Canada. The impact of double-stranded RNA (dsRNA) plant-incorporated protectants (PIPs) and dietary RNAi to non-target organisms, however, still needs further investigation. In this study, we assessed the potential risks of a Diabrotica virgifera virgifera active dsRNA to a group of predatory biological control agents, including Hippodamia convergens, Harmonia axyridis, Coleomegilla maculata, and Coccinella septempunctata. The overarching hypothesis is that the insecticidal dsRNA targeting Diabrotica virgifera virgifera has no or negligible adverse effect on lady beetles. RESULTS: A 400-bp fragment with the highest sequence similarity between target and tested species was selected as the template for dsRNA synthesis. For the dietary RNAi toxicity assay, newly hatched first instar larvae were administered with v-ATPase A dsRNAs designed from Diabrotica virgifera virgifera and the four lady beetles, respectively. A dsRNA from ß-glucuronidase (GUS), a plant gene, and H2 O were served as the negative controls. The endpoint included both sub-organismal (gene expression), and organismal (survival rate, development time, pupa and adult weight) measurements. The results from dietary RNAi toxicity assay demonstrate significantly impacts of Diabrotica virgifera virgifera-active dsRNAs on lady beetles under the worst-case scenario at both transcriptional and phenotypic level. Interestingly, substantial differences among the four lady beetle species were observed toward the ingested exogenous dsRNAs. CONCLUSION: Such differential response to dietary RNAi may shed light on the mechanisms underlying the mode-of-action of RNAi-based biopesticides. © 2020 Society of Chemical Industry.

Genetic variability of morpho-physiological response to phosphorus deficiency in Tunisian populations of Brachypodium hybridum.

Brachypodium hybridum (Poaceae) is widely distributed in the dry environments in Mediterranean basin, due to its high tolerance to drought. Investigating the natural variation of B. hybridum in response to environmental stresses is crucial for unraveling the genetic network of its stress tolerance. 79 B. hybridum lines from eight Tunisian populations were screened for their performance to low P availability using morpho-physiological parameters. ANOVA showed that treatment and population*treatment factors were the most contributors in the explained variance for the majority of parameters. A considerable population differentiation was detected in control and under P level (Qst = 0.77 vs Qst = 0.62). This suggests that B. hybridum exhibit an adaptive differential response to P deficiency related environmental conditions. Results revealed that Raouad and Sejnen lines were the most tolerant to P deficiency followed by Haouaria and Enfidha lines. The remaining populations were classified as sensitive. This pattern suggests that coastal populations were more tolerant to P deficiency than the inland ones. A slightly higher heritability was evidenced under low P level for most of traits, indicating that the direct selection under P deficiency is more reliable than an indirect one under optimal P supply.

Response of net primary production to land use and climate changes in the middle-reaches of the Heihe River Basin.

Net primary production (NPP) supplies matter, energy, and services to facilitate the sustainable development of human society and ecosystem. The response mechanism of NPP to land use and climate changes is essential for food security and biodiversity conservation but lacks a comprehensive understanding, especially in arid and semi-arid regions. To this end, taking the middle-reaches of the Heihe River Basin (MHRB) as an example, we uncovered the NPP responses to land use and climate changes by integrating multisource data (e.g., MOD17A3 NPP, land use, temperature, and precipitation) and multiple methods. The results showed that (a) land use intensity (LUI) increased, and climate warming and wetting promoted NPP. From 2000 to 2014, the LUI, temperature, and precipitation of MHRB increased by 1.46, 0.58°C, and 15.76 mm, respectively, resulting in an increase of 14.62 gC/m2 in annual average NPP. (b) The conversion of low-yield cropland to forest and grassland increased NPP. Although the widespread conversion of unused land and grassland to cropland boosted both LUI and NPP, it was not conducive to ecosystem sustainability and stability due to huge water consumption and human-appropriated NPP. Urban sprawl occupied cropland, forest, and grassland and reduced NPP. (c) Increase in temperature and precipitation generally improved NPP. The temperature decreasing <1.2°C also promoted the NPP of hardy vegetation due to the simultaneous precipitation increase. However, warming-induced water stress compromised the NPP in arid sparse grassland and deserts. Cropland had greater NPP and NPP increase than natural vegetation due to the irrigation, fertilizers, and other artificial inputs it received. The decrease in both temperature and precipitation generally reduced NPP, but the NPP in the well-protection or less-disturbance areas still increased slightly.

Peptidoglycan and Lipoteichoic Acid Induces Differential mRNA Response of Immune-Related Genes in PBMC of Crossbred, Tharparkar Cattle and Murrah Buffalo.

Subclinical mastitis, generally caused by Staphylococcus aureus, has a global economic impact all over the world. Hence, it needs to be resolved on higher priority which may be attained via. selection of mastitis resistant animals or inclusion of mastitis resistant trait into herd apart from management care. Diverse hosts with various genetic make-ups encounter pathogens in a diverse manner which in turn leads to contradicting outcome of the disease. Identification of species-wise or breed-wise differential expressed genes in response to S. aureus through relative evaluation of transcripts may be useful for judging the immuno-competency of a species or breed toward mastitis. The present study was undertaken to examine the stimulant effect of S. aureus peptidoglycan (PGN) and lipoteichoic acid (LTA) on Peripheral blood mononuclear cells (PBMC) harvested from blood samples of crossbred cattle, Tharparkar cattle, and Murrah buffaloes. After 6 h of in vitro stimulation qRT-PCR was used to measure the relative mRNA expression of TLR-2, TNF-α, IL-8, IFN-γ and IL-10 genes in stimulated and un-stimulated PBMC. The selected genes revealed significant differences in the pattern of immune response among crossbred cattle, Tharparkar cattle and Murrah buffalo in spite of the same stimulant dose.

Differential Response and Children Re-Reported to Child Protective Services: County Data From the National Child Abuse and Neglect Data System (NCANDS).

Child protection systems that implement differential response (DR) systems screen to route referrals to an investigation response (IR) or alternative response (AR). AR responses emphasize family engagement, assessment of family needs, and service linkage. Usually, AR state-level policy does not require child welfare staff to make a maltreatment determination. Jurisdictions implement DR systems differently, leading to variations in the proportion of AR cases, risk levels of cases served, and the ways families access and use services. County data from the National Child Abuse and Neglect Data System were analyzed for six states from 2004 to 2013 that implemented DR. Variation in county-level AR rates were associated with county-level re-report rates using regression models with risk adjustments for socioeconomic and other county characteristics. Counties had 3% fewer re-reports overall for each percentage increase in AR use; higher levels of AR use are related to lower levels of re-reporting. When county AR and IR cases were analyzed separately, increasing rates of AR were associated with lower re-report rates for IR cases, but higher re-report rates for AR cases. Findings for the AR and IR subgroup must be interpreted with caution as a number of technical factors may be driving these results.

Drought tolerance in alfalfa (Medicago sativa L.) varieties is associated with enhanced antioxidative protection and declined lipid peroxidation.

Drought stress is considered the most adverse factor restricting plant survival, growth, and productivity. The identification of the key adaptive mechanisms to drought stress is essential to enhance the drought resistance of plants. In this study, differential responses of three alfalfa varieties to drought, including Medicago sativa L. cv. Longzhong (drought-tolerant), Longdong (moderate drought-tolerant), and Gannong No. 3 (drought-sensitive), were comparatively studied at morphological, physio-biochemical, and transcriptional levels after a 12-day period of drought stress simulated by -1.2 MPa polyethylene glycol (PEG-6000). The results showed that prolonged drought stress dramatically decreased growth and photosynthetic capacity of three alfalfa varieties while it increased the accumulation of malondialdehyde (MDA), reactive oxygen species (ROS), osmolytes and antioxidants including reduced ascorbate and glutathione, ascorbate peroxidase (APX) activities, and gene expression of antioxidative enzymes (MsCu/Zn-SOD, MsFeSOD, MtPOD, MsGPX, MsAPX, MsMDAR, MtDHAR, and MsGR). Nine days of treatment and some key traits, including the maximum quantum yield of photosystem II (Fv/Fm), the levels of MDA, O2-, and H2O2, the redox states of ascorbate and glutathione, APX activity, and the transcript levels of MsFeSOD, MsGR, and MsMDAR, might contribute to differentiating the drought stress tolerance in alfalfa. Overall, drought-tolerant Longzhong showed the highest water retention, photosynthetic performance, and osmoregulation capacity, the lowest lipid peroxidation, and the highest antioxidant enzyme activities and gene expression, which were mainly involved in the ascorbate-glutathione cycle to maintain the balance between the generation and scavenging of intracellular ROS. These findings highlight that enhanced antioxidative protection and declined lipid peroxidation play an important role in alfalfa tolerance against drought.

Comparative Response of the Hepatic Transcriptomes of Domesticated and Wild Turkey to Aflatoxin B1.

The food-borne mycotoxin aflatoxin B1 (AFB1) poses a significant risk to poultry, which are highly susceptible to its hepatotoxic effects. Domesticated turkeys (Meleagris gallopavo) are especially sensitive, whereas wild turkeys (M. g. silvestris) are more resistant. AFB1 toxicity entails bioactivation by hepatic cytochrome P450s to the electrophilic exo-AFB1-8,9-epoxide (AFBO). Domesticated turkeys lack functional hepatic GST-mediated detoxification of AFBO, and this is largely responsible for the differences in resistance between turkey types. This study was designed to characterize transcriptional changes induced in turkey livers by AFB1, and to contrast the response of domesticated (susceptible) and wild (more resistant) birds. Gene expression responses to AFB1 were examined using RNA-sequencing. Statistically significant differences in gene expression were observed among treatment groups and between turkey types. Expression analysis identified 4621 genes with significant differential expression (DE) in AFB1-treated birds compared to controls. Characterization of DE transcripts revealed genes dis-regulated in response to toxic insult with significant association of Phase I and Phase II genes and others important in cellular regulation, modulation of apoptosis, and inflammatory responses. Constitutive expression of GSTA3 was significantly higher in wild birds and was significantly higher in AFB1-treated birds when compared to controls for both genetic groups. This pattern was also observed by qRT-PCR in other wild and domesticated turkey strains. Results of this study emphasize the differential response of these genetically distinct birds, and identify genes and pathways that are differentially altered in aflatoxicosis.

Identifying families with complex needs after an initial child abuse investigation: A comparison of demographics and needs related to domestic violence, mental health, and substance use.

Families with complex needs related to domestic violence, mental health, and substance use have some of the worst child protective services (CPS) outcomes. Although many of these families are identified during a CPS investigation and subsequently referred to home-based postinvestigation services (HBPS), many are re-reported to CPS, so it is important to understand the postinvestigation experiences of this vulnerable group. Therefore, this study compared families with and without complex needs to understand their uniquedemographics, needs, and postinvestigation outcomes. The sample consisted of 2008 caregivers who received HBPS following an initial CPS investigation. The Family Assessment Form (FAF) was used to measure family functioning in eight domains using a 1-5 scale with higher ratings representing worse functioning. Complex needs were indicated by a mean FAF score of 3 or higher for either domestic violence, mental health, or substance use. Using Pearson chi-square analyses and two-sample t-tests, comparisons were made between families with (n=836) and without (n=1172) complex needs. Half of caregivers with complex needs had a history of abuse, 25% had three to five needs, and nearly half had six to eight needs; 90% of caregivers without complex needs had zero to two needs. Furthermore, caregivers with complex needs had higher mean scores for concrete, educational, and clinical needs. These findings highlight the importance of recognizing variation among families referred to HBPS and accurate screening to ensure that families with complex needs are offered and receive services matched to their unique characteristics and needs.

T-cell epitope strength in WAP-T mouse mammary carcinomas is an important determinant in PD1/PD-L1 immune checkpoint blockade therapy.

Using the SV40 transgenic WAP-T/WAP-TNP mouse models for mammary carcinomas, we compared the response to immune checkpoint blockade therapy in tumor mice expressing either SV40 T-antigen containing the LCMV NP-epitope (T-AgNP in WAP-TNP mice), or the unmodified T-antigen (T-Ag in WAP-T mice). Specifically, we asked, whether the presence of the highly immunogenic NP-epitope in T-AgNP influences this response in comparison to the weakly immunogenic T-cell epitopes of T-Ag in WAP-T tumor mice. Treatment of WAP-TNP tumor mice with either anti-PD1 or anti-PD-L1 antibodies led to tumor regression, with anti-PD-L1 treatment being more effective. However, tumors had fully re-appeared after 21 days, indicating that CTL exhaustion had been rapidly re-established. Surprisingly, the same treatment applied to WAP-T tumor mice resulted in a significantly prolonged period of tumor regression. We provide evidence that in contrast to the weak antigenic stimuli exerted by T-cell epitopes of T-Ag, the strong antigenic stimulus of the NP-epitope in T-AgNP has a dual effect: (i) a rapid generation of active NP-specific CTLs, accompanied (ii) by accelerated CTL exhaustion. Our data support the hypothesis that the immunogenicity of tumor antigen T-cell epitopes strongly influences the success of immune checkpoint blockade therapy.