Adaptive Response Research Articles

Transcription factor networks drive perforin activity in the anti-bacterial immune response of tilapia

Perforin, produced by natural killer (NK) cells and cytotoxic T lymphocytes (CTLs), is one of the effectors of cell-mediated cytotoxicity (CMC) in vertebrates, playing a paramount role in killing target cells. However, whether and how perforin is involved in adaptive immune responses in early vertebrates remains unclear. Using Nile tilapia (Oreochromis niloticus) as a model, we investigated the characteristics of perforin in early vertebrates. Oreochromis niloticus perforin (OnPRF) possesses 2 conserved functional domains, membrane attack complex/perforin (MACPF) and protein kinase C conserved region 2 (C2) domains, although they share low amino acid sequence similarity with other homologs. OnPRF was widely expressed in various immune tissues and could respond to lymphocyte activation and T-cell activation in vitro at both the transcriptional and protein levels, indicating that it may be involved in adaptive immune responses. Furthermore, after infection with Edwardsiella piscicida and Aeromonas hydrophila, the mRNA and protein levels of OnPRF were significantly up-regulated within the adaptive immune response period. Additionally, we revealed that many transcription factors were involved in the transcriptional regulation of OnPRF, including p65, c-Fos, c-Jun, STAT1 and STAT4, and there was a synergy among these transcription factors. Overall, these findings demonstrate the involvement of OnPRF in T-cell activation and adaptive immune response in tilapia, thus providing new evidence for comprehending the evolution of immune response in early vertebrates.

Evolutionary integration of forelimb and hindlimb proportions within the bat wing membrane inhibits ecological adaptation.

Bats and birds are defined by their convergent evolution of flight, hypothesized to require the modular decoupling of wing and leg evolution. Although a wealth of evidence supports this interpretation in birds, there has been no systematic attempt to identify modular organization in the bat limb skeleton. Here we present a phylogenetically representative and ecologically diverse collection of limb skeletal measurements from 111 extant bat species. We compare this dataset with a compendium of 149 bird species, known to exhibit modular evolution and anatomically regionalized skeletal adaptation. We demonstrate that, in contrast to birds, morphological diversification across crown bats is associated with strong trait integration both within and between the forelimb and hindlimb. Different regions of the bat limb skeleton adapt to accommodate variation in distinct ecological activities, with flight-style variety accommodated by adaptation of the distal wing, while the thumb and hindlimb play an important role facilitating adaptive responses to variation in roosting habits. We suggest that the wing membrane enforces evolutionary integration across the bat skeleton, highlighting that the evolution of the bat thumb is less correlated with the evolution of other limb bone proportions. We propose that strong limb integration inhibits bat adaptive responses, explaining their lower rates of phenotypic evolution and relatively homogeneous evolutionary dynamics in contrast to birds. Powered flight, enabled by the membranous wing, is therefore not only a key bat innovation but their defining inhibition.

Mitochondrial elongation confers protection against doxorubicin-induced cardiotoxicity

Doxorubicin (DOX)-induced cardiac damage remains a leading cause of death amongst cancer survivors. DOX-induced cardiotoxicity (DIC) is mediated by disturbed mitochondrial dynamics, but it remains debated that the mechanisms by which DOX disrupted equilibrium between mitochondrial fission and fusion. In the present study, we observed DOX induced mitochondrial elongation in multiple cardiovascular cell lines. Mechanically, DOX not only downregulated the mitochondrial fusion proteins including Mitofusin 1/2 (MFN1/2) and Optic atrophy 1 (OPA1), but also induced lower motility of dynamin-related protein 1(Drp1) and its phosphorylation on 637 serine, which could inhibit mitochondrial fission. Interestingly, DOX failed to induce mitochondrial elongation in cardiomyocytes co-treated with protein kinase A (PKA) inhibitor H89 or expressing phosphodeficient Drp1-S637A variants. Besides, carbonyl cyanide 3-chlorophenylhydrazone (CCCP) was able to blocked the mitochondrial elongation induced by DOX treatment, which could be phenocopied by OPA1 knockdown. Therefore, we speculated that DOX inhibited both mitochondrial fission and fusion simultaneously, yet enabled mitochondrial fusion dominate the mitochondrial dynamics, resulting in mitochondrial elongation as the main manifestation. Notably, blocking mitochondrial elongation by inhibiting Drp1-S637 phosphorylation or OPA1 knockdown aggravated DOX-induced cardiomyocytes death. Based on these results, we propose a novel mechanistic model that DOX-induced mitochondrial elongation is attributed to the equilibrium disturbance of mitochondrial dynamics, which serves as an adaptive response and confers protection against DIC.

Tumor microenvironment activated MXene-protected Cu2O heterojunctions induce tumor-specific cuproptosis for enhanced sono-immunotherapy

The utilization of a copper ionophore to induce programmed cell death, known as cuproptosis, shows potential in augmenting the efficacy of traditional anticancer treatments and eliciting robust adaptive immune responses. Nevertheless, the non-tumor-specific release of Cu ions may initiate cuproptosis and cause irreversible damage to normal tissues. Herein, this work reports for the first time the regulation of degradation behaviors of Cu-based nanomaterials using Ti3C2Tx nanosheets as a protection layer to maximize the therapeutic effects of tumor-specific cuproptosis. A Z-scheme heterojunction termed Cu2O/Ti3C2Tx is facilely constructed by coating Ti3C2Tx nanosheets on the surface of Cu2O nanocubes. The fabrication of heterojunctions not only improves the sonodynamic and chemodynamic activities of Cu2O nanocubes owing to the manipulation of electron-hole transfer process, but also avoids the degradation of Cu2O nanocubes under normal physiological conditions. The tumor-specific released Cu ions not only realized the cascade amplification of ROS generation through Cu+-mediated Fenton-like reaction and Cu2+-facilitated GSH depletion, but also triggered cuproptosis through Cu+-induced DLAT oligomerization and mitochondrial dysfunction. More importantly, the immunosuppressive TME could be reversed by the greatly enhanced ROS levels and high-efficiency cuproptosis, ultimately inducing immunogenic cell death that promotes robust systemic immune responses for the eradication of primary tumors and suppression of distant tumors. This work provides a promising perspective for potential cancer treatment based on tumor-specific cuproptosis by controlling the degradation behaviors of Cu-based nanomaterials.

Differential gene expression of immune response in COVID-19 and its relationship with progression of COVID-19

Human immune response evolved in virus clearance and gene expression levels of immune response may be associated with progression of Coronavirus disease 2019 (COVID-19). Our current study aims to investigate the relationship between differential gene expression of immune response and progression of COVID-19. A total of 50 participants of COVID-19 group were studied, compared with 39 participants of healthy control group. There were different gene expression profiles in pathways of activation of neutrophil, defense response and adaptive immune response for COVID-19 group before treatment compared to the healthy control group. Distinct gene expression profiles showed that pathways of chemotaxis, immune response and antibacterial humoral response involved in rehabilitation of severe COVID-19 group while pathways of immune system process, defense response to virus and negative regulation of viral genome replication involved in rehabilitation of moderate COVID-19 group. Both protein expression of ATP-binding cassette transporter A1 levels and protein expression of low affinity Fc-receptor FcγRIIIb levels were significantly and positively correlated with COVID-19-IgM levels and might be suitable as biomarkers for monitoring of COVID-19. This study showed that differential gene expression of immune response predicted onset and rehabilitation of COVID-19.

Iranian farmers' response to the drought crisis: How can the consequences of drought be reduced?

Climate change (CC) is an undeniable global phenomenon, impacting various regions, including Iran. Key components of CC, including the increase in greenhouse gases, rising temperatures, and fluctuations in precipitation patterns, are expected to significantly reduce agricultural crop yields in the near future. In response, identifying effective adaptation strategies is critical for mitigating these adverse effects. This study investigates the role of environmental values, risk perception, and psychological distance in shaping Iranian farmers’ adaptation strategies to CC. A sample of 390 farmers from Shushtar County in southwestern Iran was selected through a multi-stage stratified sampling method. Using structural equation modeling (SEM), the analysis revealed complex interrelationships between environmental values (biospheric, altruistic, and egoistic), beliefs, risk perception, psychological distance, and farmers' adaptation responses to CC. Furthermore, the results indicated that the study variables explain 67.6% of the variance in farmers' adaptive behaviors, with belief in CC emerging as the most influential factor. These findings not only enrich the current body of literature but also provide actionable insights for policymakers to foster adaptive strategies among farmers.

Antifungal activity and mechanism of mefentrifluconazole against Magnaporthe grisea causing rice blast

Rice blast, caused by Magnaporthe grisea, is one of the most destructive diseases of rice worldwide. Mefentrifluconazole, a novel isopropanol triazole fungicide, exhibits excellent bioactivity to a wide range of fungi. However, its antifungal activity against M. grisea is not well studied. In this study, the sensitivity of 103 M. oryzae strains to mefentrifluconazole was determined by mycelial growth rate method, and the effect of mefentrifluconazole on the biochemical and physiological characteristers was examined. The results indicated that mefentrifluconazole exhibited excellent inhibitory activity against M. oryzae with EC50 values of 103 M. oryzae strains tested ranging from 0.363 to 1.576 μg/mL, and the average EC50 value of 0.958 ± 0.298 μg/mL. After mefentrifluconazole treatment, the apical branches of M. oryzae mycelia increased and the mycelia became distorted, twisted and ruptured. In addition, mefentrifluconazole increased relative conductivity, disrupted cell wall and membrane integrity, and significantly reduced ergosterol content. The expression levels of demethylation inhibitor resistance-associated genes Cyp51A, ABC6 and MFS1 were all significantly upregulated, suggesting an adaption response to mefentrifluconazole of M. oryzae. Furthermore, the results of pot experiment showed that mefentrifluconazole provided >70% control efficacy against rice blast at 300 μg/mL, surpassing the performance of carbendazim, prochloraz and azoxystrobin at the same concentration. Overall, this study demonstrated the strong inhibitory activity of mefentrifluconazole against M. oryzae and the excellent efficacy in controlling rice blast, thus providing new sights into rice blast control as well as the practical application of mefentrifluconazole.

Fractional-Order Mathematical Modeling of Breast Cancer: Comparing Adaptive Immune Responses and Estrogen Dynamics with Experimental Data

Breast cancer is a significant global health concern that requires innovative approaches to understand its behavior and improve treatment strategies. This paper introduces a new fractional-order mathematical model to explain the complex dynamics of breast cancer progression, including adaptive immune responses and estrogen dynamics. Utilizing Caputo fractional derivatives, our model reveals insights into the impact of fractional-order dynamics on cancer cell populations. Simulation results demonstrate a notable increase in cell populations with higher fractional orders, suggesting heightened aggressiveness, while lower orders correspond to subdued progression. Unlike traditional integer-order models, fractional-order derivatives offer a more nuanced depiction of nonlinear dynamics, crucial for capturing the complexities of cancer progression. Importantly, our findings underscore the potential clinical relevance of fractional-order models in informing personalized treatment strategies, particularly through the modulation of estrogen levels. By integrating treatment considerations, such as hormone therapy, our model holds promise for advancing precision medicine approaches tailored to individual patient characteristics.

Exploring therapeutic responsiveness: a comparative textual analysis across different models

The purpose of this study is to examine therapeutic responsiveness across three different therapeutic models. The construct of responsiveness consists of two conceptual features: optimal responsiveness, which involves adapting therapist behavior to the unique therapeutic relationship, and appropriate responsiveness, a more refined concept. While aligned with interpersonal principles, the responsiveness construct challenges prevailing statistical methods by emphasizing the therapist’s adaptive responses. A comparative analysis of Gestalt, psychodynamic, and systemic therapies revealed unique patterns of responsiveness within each model, ranging from an emphasis on empathy and intuition to the significance of countertransference. Methodologically, a literature review and textual analysis using Atlas.ti allowed for nuanced exploration. The results also revealed a core commonality—"experience”—across these models, positioning responsiveness as an “extra-specific” factor amidst shared conceptual ground. In conclusion, this study sheds light on the nuances of responsiveness, which is central to advancing psychotherapeutic practice in an evolving landscape. An in-depth examination of the construct of responsiveness helps identify therapist characteristics that can be enhanced, enriched, and supported during training and supervision.

Neuronal connectivity, behavioral, and transcriptional alterations associated with the loss of MARK2.

Neuronal connectivity is essential for adaptive brain responses and can be modulated by dendritic spine plasticity and the intrinsic excitability of individual neurons. Dysregulation of these processes can lead to aberrant neuronal activity, which has been associated with numerous neurological disorders including autism, epilepsy, and Alzheimer's disease. Nonetheless, the molecular mechanisms underlying abnormal neuronal connectivity remain unclear. We previously found that the serine/threonine kinase Microtubule Affinity Regulating Kinase 2 (MARK2), also known as Partitioning Defective 1b (Par1b), is important for the formation of dendritic spines invitro. However, despite its genetic association with several neurological disorders, the invivo impact of MARK2 on neuronal connectivity and cognitive functions remains unclear. Here, we demonstrate that the loss of MARK2 invivo results in changes to dendritic spine morphology, which in turn leads to a decrease in excitatory synaptic transmission. Additionally, the loss of MARK2 produces substantial impairments in learning and memory, reduced anxiety, and defective social behavior. Notably, MARK2 deficiency results in heightened seizure susceptibility. Consistent with this observation, electrophysiological analysis of hippocampal slices indicates underlying neuronal hyperexcitability in MARK2-deficient neurons. Finally, RNAseq analysis reveals transcriptional changes in genes regulating synaptic transmission and ion homeostasis. These results underscore the invivo role of MARK2 in governing synaptic connectivity, neuronal excitability, and cognitive functions.

RNA-Seq Reveals Transcriptome Changes Following Zika Virus Infection in Fetal Brains in c-Flip Knockdown Mice

The FADD-like interleukin-1β converting enzyme (FLICE)-inhibitory protein (c-FLIP) plays a crucial role in various biological processes, including apoptosis and inflammation. However, the complete transcriptional profile altered by the c-FLIP is not fully understood. Furthermore, the impact of the c-FLIP deficiency on the transcriptome during a Zika virus (ZIKV) infection, which induces apoptosis and inflammation in the central nervous system (CNS), has not yet been elucidated. In this study, we compared transcriptome profiles between wild-type (WT) and the c-Flip heterozygous knockout mice (c-Flip+/−) fetal heads at embryonic day 13.5 from control and PBS-infected WT dams mated with c-Flip+/− sires. In the non-infected group, we observed differentially expressed genes (DEGs) mainly involved in embryonic development and neuron development. However, the ZIKV infection significantly altered the transcriptional profile between WT and the c-Flip+/− fetal heads. DEGs in pattern recognition receptor (PRR)-related signaling pathways, such as the RIG-I-like receptor signaling pathway and Toll-like receptor signaling pathway, were enriched. Moreover, the DEGs were also enriched in T cells, indicating that the c-FLIP participates in both innate and adaptive immune responses upon viral infection. Furthermore, our observations indicate that DEGs are associated with sensory organ development and eye development, suggesting a potential role for the c-FLIP in ZIKV-induced organ development defects. Overall, we have provided a comprehensive transcriptional profile for the c-FLIP and its modulation during a ZIKV infection.

Therapeutic Immunomodulation of Tumor-Lymphatic Crosstalk via Intratumoral Immunotherapy.

Intra- and peritumoral lymphatics and tumor-draining lymph nodes play major roles in mediating the adaptive immune response to cancer immunotherapy. Despite this, current paradigms of clinical cancer management seldom seek to therapeutically modulate tumor-lymphatic immune crosstalk. This review explores recent developments that set the stage for how this regulatory axis can be therapeutically manipulated, with a particular emphasis on tumor-localized immunomodulation. Building on this idea, the nature of tumor-lymphatic immune crosstalk and relevant immunotherapeutic targets and pathways are reviewed, with a focus on their translational potential. Engineered drug delivery systems that enhance intratumoral immunotherapy by improving drug delivery to both the tumor and lymph nodes are also highlighted.

Effects of intensive and conventional farming on oxidative stress and meat quality biomarkers in holstein and simmental cattle

This study investigates the intricate factors influencing meat quality, including breed, rearing conditions, and processing, with a primary focus on oxidative stress in Holstein Friesian and Simmental cattle within conventional and intensive production systems. A notable difference in oxidative stress was found between animals subjected to intensive-farming versus conventional practices, with Holstein cattle showing a more pronounced antioxidant gene response than Simmental. The analysis revealed that intensive rearing conditions resulted in increased DNA repair activity and expression of stress-response proteins like heat shock proteins, suggestive of greater cellular damage and an adaptive stress response. Muscle tissue analyses, revealed a clear distinction in gene expression associated with meat quality between the breeds and the type of farming system. A negative correlation emerged between oxidative stress levels and genes related to muscle development, which affects meat quality. Intensive farming conditions altered the expressions of apoptotic proteins, impacting meat quality at the molecular level. These results underscore the profound effect rearing conditions have on meat quality, driven by stress-related molecular responses. This highlights the need for further research into the influence of husbandry practices on animal welfare and meat quality, with the intention of developing strategies to mitigate the negative consequences of intensive-farming.

Possible involvement of Toll-like receptor 8-positive monocytes/macrophages in the pathogenesis of Sjögren’s disease

BackgroundSjögren’s disease (SjD) is an autoimmune disease marked by lymphocytic infiltration of salivary and lacrimal glands, leading to glandular dysfunction, where CD4-positive helper T (Th) cells and their cytokines are crucial in the pathogenesis. Recent studies have demonstrated that Toll-like receptors (TLRs), particularly those recognizing immune complexes containing DNA and RNA, contribute to Th cell activation in various autoimmune diseases. This study explores the expression and function of these TLRs in SjD.MethodsDNA microarray analysis of salivary gland tissue from six SjD patients and real-time PCR (n = 32) was used to identify overexpressed TLRs. Single-cell RNA sequencing (scRNA-seq) was performed using tissue lesions and integrated with published scRNA-seq data from tissues and peripheral blood mononuclear cells to examine gene expression in macrophages and monocytes. Finally, multi-color immunofluorescence staining was conducted to confirm TLR8 expression and function in SjD lesions (n = 19).ResultsDNA microarray analysis revealed the up-regulation of TLR8, along with other TLRs and innate immune response genes in SjD. Real-time PCR showed significant up-regulation of TLR7 and TLR8. TLR8 up-regulated in both analyses. In scRNA-seq analysis, the TLR8-expressing cluster comprised macrophages and monocytes, which also produced T cell activation genes like CD86. TLR8-positive macrophages infiltrated inflammatory sites and frequently expressed CD86 in quantitative imaging approaches.ConclusionsThese results suggest that infiltrating monocytes and macrophages may produce cytokines and chemokines through TLR8 stimulation, potentially enhancing B7 molecule expression, promoting the adaptive immune response, and contributing to SjD pathogenesis.

Adaptive Changes in Human Leukocytes in Response to a Long-Term Stay in Antarctica

Oxidative stress and aging are known to alter the copy number (CN) of satellite III repeat (1q12) (SatIII(1q)) and telomeric repeat (TR) in the DNA of human cells. The extreme conditions of Antarctica could potentially affect the CN of these repeats in human blood cells, which may be associated with inhibition of the antioxidant system and activation of apoptosis. In this work, we analyzed the CN of ribosomal DNA (rDNA), SatIII(1q), and TR repeats in the leukocytes of 11 male members of the expedition to Vostok station in 2019–2020. To observe dynamic changes in the number of repeating elements of the genome and the degree of their oxidation, six blood samples were taken: before arrival in Antarctica, after 27, 85, 160, 270, and 315 days of wintering. To analyze adaptive changes, the expression levels of the BAX, BCL2, NOX4, NRF2, SOD1, and HIF1 genes were measured. We detected a decrease in SatIII(1q) CN and an increase in TR CN against the background of a stable rDNA CN in human blood cells during wintering. These changes, along with a decrease in the 8-oxodG in DNA, are associated with an increase in the activity of the NOX4 gene, a decrease in the activity of the NRF2 gene, and an increase in the expression of the proapoptotic protein BAX. Thus, wintering in Antarctica stimulates an adaptive response in the human body, which includes increased elimination from the bloodstream of “ballast” cells with a high level of DNA oxidation, a high SatIII(1q) content, and a low TR content. An increase in ROS levels due to chronic activation of the NOX4 gene along with the blocked NRF2 gene may play a significant role in the development of the response.

Comparative Metabolomic Analysis Reveals the Impact of the Photoperiod on the Hepatopancreas of Chinese Grass Shrimp (Palaemonetes sinensis)

The photoperiod is a key environmental factor that in crustaceans influences development, feeding, and metabolism. In this study, liquid chromatography-tandem mass spectrometry was used to examine metabolic changes in Palaemonetes sinensis under different photoperiods. Our results showed that key metabolic pathways, such as linoleic acid metabolism, axon regeneration, pyrimidine metabolism, and cortisol synthesis, were significantly altered under both constant light (24L:0D) and constant darkness (0L:24D) compared with natural light conditions. The photoperiod notably affected the digestive and metabolic functions of P. sinensis. Most metabolic pathways were downregulated under full darkness and full light conditions, suggesting that inhibition of metabolism is a potential adaptive response. Furthermore, enzyme assays revealed significant variations in trypsin, lipase, and amylase activity across different photoperiods, highlighting the profound impact of light conditions on digestive functions. These findings suggest that extreme light conditions may negatively impact the metabolic and digestive functions of P. sinensis. This study provides new insights into the adaptive mechanisms of P. sinensis in response to photoperiod changes and offers valuable information for optimizing aquaculture practices to enhance the health and growth performance of this crustacean.

IMPLEMENTING FLOOD-RESISTANT DESIGN STRATEGIES IN COASTAL REGIONS

This systematic review synthesizes findings from 85 articles to examine flood-resistant design strategies in coastal regions, emphasizing an integrated approach that combines traditional engineering solutions, nature-based strategies, green infrastructure, adaptive design, and predictive modeling. The review identifies a continuing reliance on engineered defenses, such as seawalls and automated floodgates, which have proven effective but are limited in addressing the escalating impact of climate change. Findings highlight the growing importance of nature-based solutions—wetlands, mangroves, and coral reefs—that not only mitigate flood risks but also enhance biodiversity and long-term sustainability. Green infrastructure, including permeable pavements and rain gardens, emerges as a valuable urban solution, although it faces implementation challenges in densely populated areas. The integration of predictive modeling and real-time data is transforming flood management by enabling proactive and adaptive responses, though these technologies remain financially inaccessible for many regions. Comparative analysis underscores that flood-resilient design is highly context-dependent, with successful practices varying based on local geography, resources, and socio-economic factors. This review concludes that future flood-resilient infrastructure must prioritize adaptable, sustainable, and region-specific solutions, highlighting the need for cross-disciplinary collaboration and continued policy support to enhance flood resilience and protect vulnerable coastal communities against the effects of climate change.

Cell aggregation mediated by ACE2 deletion in Candida auris modulates fungal colonization and host immune responses in the skin.

Candida auris is an emerging multi-drug-resistant fungal pathogen that colonizes the skin and causes invasive infections in hospitalized patients. Multi-cellular aggregative phenotype is widely reported in the C. auris isolates, but its role in skin colonization and host immune response is not yet known. In this study, we generated aggregative phenotype by deleting the ACE2 gene in C. auris and determined the fungal colonization and host immune response using an intradermal mouse model of C. auris skin infection. Our results indicate that mice infected with ace2Δ strain had significantly lower fungal load after 3 and 14 days post-infections compared to the non-aggregative wild-type and the ACE2 reintegrated strain. The colonization of ace2Δ is associated with increased recruitment of CD11b+ Ly6G+ neutrophils and decreased accumulation of CD11b+ Ly6 Chi inflammatory monocytes and CD11b+ MHCII+ CD64+ macrophages. Furthermore, Th17 cells and type 3 innate lymphoid cells (ILCs) were significantly increased in the skin tissue of ace2Δ infected mice. Our findings suggest that aggregative phenotype mediated by ACE2 deletion in C. auris induces potent neutrophil and IL-17-mediated immune response and reduces fungal colonization in the skin.IMPORTANCEC. auris is a rapidly emerging fungal pathogen that can colonize hospitalized patients, especially in skin tissue, and cause invasive infections. C. auris isolates exhibit morphological heterogeneity, and the multicellular aggregative phenotype of C. auris is reported frequently in clinical settings. Understanding the role of fungal morphotypes in colonization, persistence, and immune response in the skin microenvironment will have potential applications in clinical diagnosis and novel preventive and therapeutic measures. Here, we utilized the murine model of intradermal infection and determined that the aggregative phenotype of C. auris as the result of ACE2 gene deletion elicits potential innate and adaptive immune responses in mice. These observations will help explain the differences in the skin colonization and immune responses of the aggregative morphotype of C. auris and open the door to developing novel antifungal therapeutics.

Interleukins: Role in cancer and its immunotherapy

Interleukins are a very important family of cytokines; they are the messengers that assist immune cells to communicate with each other. Interleukins plays a pivotal role in innate and adaptive immune responses by balancing immune cell proliferation, differentiation and regulation. Interleukins aid immune cells in killing cancer cells while simultaneously assisting cancer cells in evading the immune response which leads tumor formation. Some interleukins are very effective at activating effector immune cells to kill cancer cells and also used for cancer immunotherapy. Interleukins are utilized in cancer immunotherapy alone or in combination with other therapies such as CAR-T, checkpoint inhibitors, or chemotherapy. In this review, we will explore the role of different interleukins in cancer and how researchers modified and therapeutically used them to treat cancer (e.g. IL-2, IL-12, IL-15, IL-17, IL-6, IL-18 etc.,).

Performance of a Global Functional Assay Based on Interferon-γ Release to Predict Infectious Complications and Cancer After Kidney Transplantation

The QuantiFERON-Monitor assay (QTF-Monitor) is intended to assess innate and adaptive immune responses by quantifying interferon (IFN)-γ release upon whole blood stimulation with a TLR7/8 agonist and an anti-CD3 antibody. We performed the QTF-Monitor in 126 kidney transplant recipients (KTRs) at different points during the first 6 post-transplant months. The primary outcome was overall infection, whereas secondary outcomes included bacterial infection, opportunistic infection and de novo cancer. The association between IFN-γ production and outcomes was analyzed as “low” immune responses (<15 IU/mL) and as a continuous variable to explore alternative thresholds. There were no significant differences in the occurrence of overall infection according to the QTF-Monitor at any monitoring point. Regarding secondary outcomes, KTRs with a low response at week 2 experienced a higher incidence of bacterial infection (50.8% versus 24.4%; P-value = 0.006). Low response at month 1 was also associated with opportunistic infection (31.6% versus 14.3%; P-value = 0.033). The discriminative capacity of IFN-γ levels was poor (areas under the ROC curve: 0.677 and 0.659, respectively). No differences were observed for the remaining points or post-transplant cancer. In conclusion, the QTF-Monitor may have a role to predict bacterial and opportunistic infection in KTRs when performed early after transplantation.