Alpha-synuclein interaction with mitochondria is the final mechanism of ferroptotic death induced by erastin in SH-SY5Y cells.

Ferroptosis has been characterized as a form of iron-dependent regulated cell death accompanied by an accumulation of reactive oxygen species and lipid oxidation products along with typical morphological alterations in mitochondria. Ferroptosis is activated by diverse triggers and inhibited by ferrostatin-1 and liproxstatin-1, apart from iron chelators and several antioxidants, and the process is implicated in multiple pathological conditions. There are, however, certain ambiguities about ferroptosis, especially regarding the final executioner of cell death subsequent to the accumulation of ROS. This study uses a typical inducer of ferroptosis such as erastin on SH-SY5Y cells, and shows clearly that ferroptotic death of cells is accompanied by the loss of mitochondrial membrane potential and intracellular ATP content along with an accumulation of oxidative stress markers. All these are prevented by ferrostatin-1 and liproxstatin-1. Additionally, cyclosporine A prevents mitochondrial alterations and cell death induced by erastin implying the crucial role of mitochondrial permeability transition pore (mPTP) activation in ferroptotic death. Furthermore, an accumulation of α-synuclein occurs during erastin induced ferroptosis which can be inhibited by ferrostatin-1 and liproxstatin-1. When the knock-down of α-synuclein expression is performed by specific siRNA treatment of SH-SY5Y cells, the mitochondrial impairment and ferroptotic death of the cells induced by erastin are markedly prevented. Thus, α-synuclein through the involvement of mPTP appears to be the key executioner protein of ferroptosis induced by erastin, but it needs to be verified if it is a generalized mechanism of ferroptosis by using other inducers and cell lines.

Covalent-Organic Framework-Based Materials in Theranostic Applications: Insights into Their Advantages and Challenges.

Nanomedicine has been essential in bioimaging and cancer therapy in recent years. Nanoscale covalent-organic frameworks (COFs) have been growing as an adequate classification of biomedical nanomaterials with practical application prospects because of their increased porosity, functionality, and biocompatibility. The high sponginess of COFs enables the incorporation of distinct imaging and therapeutic mechanisms with a better loading efficiency. Nevertheless, preliminary biocompatibility limits their possibility for clinical translation. Thus, cutting-edge nanomaterials with high biocompatibility and improved therapeutic efficiency are highly expected to fast-track the clinical translation of nanomedicines. The inherent effects of nanoscale COFs, such as proper size, modular pore geometry and porosity, and specific postsynthetic transformation through simple organic changes, make them particularly appealing for prospective nanomedicines. The organic building blocks of COFs may also be postmodified for particular binding to biomarkers. The exceptional features of COFs cause them to be an encouraging nanocarrier for bioimaging and therapeutic applications. In this review, we have systematically discussed the advances of COFs in the field of theranostics by providing essential features of COFs along with their synthetic methods. Further, the applications of COFs in the field of theranostics (such as drug delivery systems, photothermal, and photodynamic therapy) are discussed in detail with the help of available literature to date. Furthermore, the advantages of COFs over other materials for therapeutics and drug delivery are discussed. Finally, the review concludes with potential future COF applications in the theranostic field.

Polymer-mediated nanoformulations: a promising strategy for cancer immunotherapy.

Engineering polymer-based nano-systems have attracted many researchers owing to their unique qualities like shape, size, porosity, mechanical strength, biocompatibility, and biodegradability. Both natural and synthetic polymers can be tuned to get desired surface chemistry and functionalization to improve the efficacy of cancer therapy by promoting targeted delivery to the tumor site. Recent advancements in cancer immunoediting have been able to manage both primary tumor and metastatic lesions via activation of the immune system. The combinations of nano-biotechnology and immunotherapeutic agents have provided positive outcomes by enhancing the host immune response in cancer therapy. The nanoparticles have been functionalized using antibodies, targeted antigens, small molecule ligands, and other novel agents that can interact with biological systems at nanoscale levels. Several polymers, such as polyethylene glycol (PEG), poly(lactic-co-glycolic acid) (PLGA), poly(ε-caprolactone) (PCL), and chitosan, have been approved by the Food and Drug Administration for clinical use in biomedicine. The polymeric nanoformulations such as polymers-antibody/antigen conjugates and polymeric drug conjugates are currently being explored as nanomedicines that can target cancer cells directly or target immune cells to promote anti-cancer immunotherapy. In this review, we focus on scientific developments and advancements on engineered polymeric nano-systems in conjugation with immunotherapeutic agents targeting the tumor microenvironment to improve their efficacy and the safety for better clinical outcomes.

Chitosan-PEI passivated carbon dots for plasmid DNA and miRNA-153 delivery in cancer cells.

These days carbon dots have been developed for multiple biomedical applications. In the current study, the transfection potential of synthesized carbon dots from single biopolymers such as chitosan, PEI-2kDa, and PEI-25kDa (CS-CDs, PEI2-CDs, and PEI25-CDs) and by combining two biopolymers (CP2-CDs and CP25-CDs) through a bottom-up approach have been investigated. The characterization studies revealed successful synthesis of fluorescent, positively charged carbon dots <20 nm in size. Synthesized carbon dots formed a stable complex with plasmid DNA (EGFP-N1) and miRNA-153 that protected DNA/miRNA from serum-induced degradation. In-vitro cytotoxicity analysis revealed minimal cytotoxicity in cancer cell lines (A549 and MDA-MB-231). In-vitro transfection of EGFP-N1 plasmid DNA with PEI2-CDs, PEI25-CDs and CP25-CDs demonstrated that these CDs could strongly transfect A549 and MDA-MB-231 cells. The highest EGFP-N1 plasmid transfection efficiency was observed with PEI2-CDs at a weight ratio of 32:1. PEI25-CDs polyplex showed maximum transfection at a weight ratio of 8:1 in A549 at a weight ratio of 16:1 in MDA-MB-231 cells. CP25-CDs exhibited the highest transfection at a weight ratio of 16:1 in both cell lines. The in-vitro transfection of target miRNA, i.e., miR-153 in A549 and MDA-MB-231 cells with PEI2-CDs, PEI25-CDs, and CP25-CDs suggested successful transfer of miR-153 into cells which induced significant cell death in both cell lines. Importantly, CS-CDs and CP2-CDs could be tolerated by cells up to 200 µg/mL concentration, while PEI2-CDs, PEI25-CDs, and CP25-CDs showed non-cytotoxic behavior at low concentrations (25 µg/mL). Together, these results suggest that a combination of carbon dots synthesized from chitosan and PEI (CP25-CDs) could be a novel vector for transfection nucleic acids that can be utilized in cancer therapy.

Sustainable Nanoparticles from Stephania glabra and Analysis of Their Anticancer Potential on 2D and 3D Models of Prostate Cancer.

In pursuit of a novel effective treatment for prostate cancer, methanolic extract of Stephania glabra tubers (Sg-ME) was utilized to fabricate silver (Sg-AgNP), copper oxide (Sg-CuONP), and silver-copper bimetallic nanoparticles (Sg-BNP). The characterization of the nanoparticles confirmed spherical shape with average diameters of 30.72, 32.19, and 25.59 nm of Sg-AgNP, Sg-CuONP, and Sg-BNP, respectively. Interestingly, these nanoparticles exhibited significant cytotoxicity toward the prostate cancer (PC3) cell line while being non-toxic toward normal cells. The nanoparticles were capable of inducing apoptosis in PC3 cells by enhancing reactive oxygen species (ROS) generation and mitochondrial depolarization. Furthermore, the shrinkage of 3D prostate tumor spheroids was observed after 4 days of treatment with these green nanoparticles. The 3D model system was less susceptible to nanoparticles as compared to the 2D model system. Sg-BNP showed the highest anticancer potential on 2D and 3D prostate cancer models.

Exosomal miRNAs as Next-generation Therapy Vehicles in Breast Cancer.

The second most pervasive cancer affecting the survival of women across the world is breast cancer. One of the biggest challenges in breast cancer treatment is the chemoresistance of cancer cells to various medications after some time. Therefore, highly specific blood-based biomarkers are required for early breast cancer diagnosis to overcome chemoresistance and improve patient survival. These days, exosomal miRNAs have attracted much attention as early diagnostic blood-based biomarkers because of their high stability, secretion from malignant tumor cells, and excellent specificity for different breast cancer subtypes. In addition, exosomal miRNAs regulate cell proliferation, invasion, metastasis, and apoptosis by binding to the 3'UTR of their target genes and limiting their production. This review focuses on the functions of exosomal miRNAs in tumorigenesis via targeting multiple signaling pathways as well as chemosensitivity and resistance mechanisms. In addition, the growing pieces of evidence discussed in this review suggest that circulating exosomal miRNAs could be utilized as potential next-generation therapeutic target vehicles in the treatment of breast cancer.

Factor structure and measurement invariance of Schizotypal Personality Questionnaire-Brief Revised (Updated) in India.

AIM: Schizotypal Personality Questionnaire-Brief Revised-Updated (SPQ-BRU) is an easy-to-conduct, theoretically consistent, and psychometrically better measure of schizotypal personality. However, its study is limited to developed countries. Thus, in the present study, we tested the factor structure and measurement invariance of SPQ-BRU in India. METHODS: A sample of 734 college students was selected from two sites (n = 614 from Muzaffarnagar in western Uttar Pradesh and n = 120 from Guhana in Haryana). Confirmatory factor analysis was used to test the good fitness of the different models of SPQ-BRU and the measurement invariance across sex and region. RESULTS: The first-order nine-factor model was a better-fit model (among a set of first-order and second-order models), whereas the second-order three-factor model was a more parsimonious good-fit model of SPQ-BRU. The nine-factor model was strongly invariant across sex and region. Women had higher social anxiety, ideas of reference, and lower constricted affect than men. Moreover, the Gohana sample was higher on several schizotypal personality facades than the Muzaffarnagar sample. CONCLUSIONS: The present study supported the cross-cultural validity of schizotypal personality and partially established a reliable and valid SPQ-BRU-Hindi language version.

Application of curcumin nanoformulations to target folic acid receptor in cancer: Recent trends and advances.

Curcumin, derived from turmeric, has a strong anticancer potential known for millennia. The development of this phytochemical as a medicine has been hampered by several significant deficiencies, including its poor water solubility and low bioavailability. This review article discusses possibilities to overcome these bottlenecks by focusing on this natural polyphenol's nanoformulation. Moreover, preparation of curcumin conjugates containing folates as ligands for folic acid receptors can add a new important dimension in this field, allowing specific targeting of cancer cells, considering the significantly higher expression of these receptors in malignant tissues compared to normal cells. It is highly expected that simultaneous improvement of different aspects of curcumin in fighting against such a complex and multifaceted disease like cancer. Therefore, we can better comprehend cancer biology by developing a mechanistic understanding of curcumin, which will also inspire the scientific community to develop new pharmacological models, and exploration of emerging directions to revitalize application of natural products in cancer therapy.

Novel Biocompatible Green Silver Nanoparticles Efficiently Eliminates Multidrug Resistant Nosocomial Pathogens and Mycobacterium Species.

Bacterial infection is a major crisis of 21st era and the emergence of multidrug resistant (MDR) pathogens cause significant health problems. We developed, green chemistry-based silver nanoparticles (G-Ag NPs) using Citrus pseudolimon fruit peel extract. G-Ag NPs has a spherical shape in the range of ~ 40 nm with a surface charge of - 31 Mv. This nano-bioagent is an eco-friendly tool to combat menace of MDR. Biochemical tests prove that G-Ag NPs are compatible with human red blood cells and peripheral blood mononuclear cells. There have been many reports on the synthesis of silver nanoparticles, but this study suggests a green technique for making non-cytotoxic, non-hemolytic organometallic silver nanoparticles with a high therapeutic index for possible use in the medical field. On the same line, G-Ag NPs are very effective against Mycobacterium sp. and MDR strains including Escherichia coli, Klebsiella species, Pseudomonas aeruginosa, and Acinetobacter baumannii isolated from patient samples. Based on it, we filed a patent to Indian Patent Office (reference no. 202111048797) which can revolutionize the prevention of biomedical device borne infections in hospital pre/post-operated cases. This work could be further explored in future by in vivo experimentation with mice model to direct its possible clinical utility. Supplementary Information: The online version contains supplementary material available at 10.1007/s12088-023-01061-0.

Significance of an Electrochemical Sensor and Nanocomposites: Toward the Electrocatalytic Detection of Neurotransmitters and Their Importance within the Physiological System.

A prominent neurotransmitter (NT), dopamine (DA), is a chemical messenger that transmits signals between one neuron to the next to pass on a signal to and from the central nervous system (CNS). The imbalanced concentration of DA may cause numerous neurological sicknesses and syndromes, for example, Parkinson's disease (PD) and schizophrenia. There are many types of NTs in the brain, including epinephrine, norepinephrine (NE), serotonin, and glutamate. Electrochemical sensors have offered a creative direction to biomedical analysis and testing. Researches are in progress to improve the performance of sensors and develop new protocols for sensor design. This review article focuses on the area of sensor growth to discover the applicability of polymers and metallic particles and composite materials as tools in electrochemical sensor surface incorporation. Electrochemical sensors have attracted the attention of researchers as they possess high sensitivity, quick reaction rate, good controllability, and instantaneous detection. Efficient complex materials provide considerable benefits for biological detection as they have exclusive chemical and physical properties. Due to distinctive electrocatalytic characteristics, metallic nanoparticles add fascinating traits to materials that depend on the material's morphology and size. Herein, we have collected much information on NTs and their importance within the physiological system. Furthermore, the electrochemical sensors and corresponding techniques (such as voltammetric, amperometry, impedance, and chronoamperometry) and the different types of electrodes' roles in the analysis of NTs are discussed. Furthermore, other methods for detecting NTs include optical and microdialysis methods. Finally, we show the advantages and disadvantages of different techniques and conclude remarks with future perspectives.

Aberrant protein glycosylation: Implications on diagnosis and Immunotherapy.

Glycosylation-mediated post-translational modification is critical for regulating many fundamental processes like cell division, differentiation, immune response, and cell-to-cell interaction. Alterations in the N-linked or O-linked glycosylation pattern of regulatory proteins like transcription factors or cellular receptors lead to many diseases, including cancer. These alterations give rise to micro- and macro-heterogeneity in tumor cells. Here, we review the role of O- and N-linked glycosylation and its regulatory function in autoimmunity and aberrant glycosylation in cancer. The change in cellular glycome could result from a change in the expression of glycosidases or glycosyltransferases like N-acetyl-glucosaminyl transferase V, FUT8, ST6Gal-I, DPAGT1, etc., impact the glycosylation of target proteins leading to transformation. Moreover, the mutations in glycogenes affect glycosylation patterns on immune cells leading to other related manifestations like pro- or anti-inflammatory effects. In recent years, understanding the glycome to cancer indicates that it can be utilized for both diagnosis/prognosis as well as immunotherapy. Studies involving mass spectrometry of proteome, site- and structure-specific glycoproteomics, or transcriptomics/genomics of patient samples and cancer models revealed the importance of glycosylation homeostasis in cancer biology. The development of emerging technologies, such as the lectin microarray, has facilitated research on the structure and function of glycans and glycosylation. Newly developed devices allow for high-throughput, high-speed, and precise research on aberrant glycosylation. This paper also discusses emerging technologies and clinical applications of glycosylation.

GLUT inhibitor WZB117 induces cytotoxicity with increased production of amyloid-beta peptide in SH-SY5Y cells preventable by beta-hydroxybutyrate: implications in Alzheimer's disease.

BACKGROUND: Inhibitors of glucose transporters are being explored as potential anti-cancer drugs. Decreased cerebral glucose utilization with reduced levels of several glucose transporters is also an important pathogenic signature of neurodegeneration of Alzheimer's disease, but its exact role in the pathogenesis of this disease is not established. We explored in an experimental model if inhibitors of glucose transporters could lead to altered amyloid-beta homeostasis, mitochondrial dysfunction, and neuronal death, which are relevant in the pathogenesis of Alzheimer's disease. METHODS: SH-SY5Y cells (human neuroblastoma cell line) were exposed to an inhibitor (WZB117) of several types of glucose transporters. We examined the effects of glucose hypometabolism on SH-SY5Y cells in terms of mitochondrial functions, production of reactive oxygen species, amyloid-beta homeostasis, and neural cell death. The effect of ß-hydroxybutyrate in ameliorating the effects of WZB117 on SH-SY5Y cells was also examined. RESULTS: We observed that exposure of SH-SY5Y cells to WZB117 caused mitochondrial dysfunction, increased production of reactive oxygen species, loss of cell viability, increased expression of BACE 1, and intracellular accumulation of amyloid ß peptide (Aß42). All the effects of WZB117 could be markedly prevented by co-treatment with ß-hydroxybutyrate. Cyclosporine A, a blocker of mitochondrial permeability transition pore (mPTP) activation, could not prevent cell death caused by WZB117. CONCLUSION: Results in this neuroblastoma model have implications for the pathogenesis of Alzheimer's disease and warrant further explorations of WZB117 in primary cultures of neurons and experimental animal models.

Strengthening microbial cell factories for efficient production of bioactive molecules.

High demand of bioactive molecules (food additives, antibiotics, plant growth enhancers, cosmetics, pigments and other commercial products) is the prime need for the betterment of human life where the applicability of the synthetic chemical product is on the saturation due to associated toxicity and ornamentations. It has been noticed that the discovery and productivity of such molecules in natural scenarios are limited due to low cellular yields as well as less optimized conventional methods. In this respect, microbial cell factories timely fulfilling the requirement of synthesizing bioactive molecules by improving production yield and screening more promising structural homologues of the native molecule. Where the robustness of the microbial host can be potentially achieved by taking advantage of cell engineering approaches such as tuning functional and adjustable factors, metabolic balancing, adapting cellular transcription machinery, applying high throughput OMICs tools, stability of genotype/phenotype, organelle optimizations, genome editing (CRISPER/Cas mediated system) and also by developing accurate model systems via machine-learning tools. In this article, we provide an overview from traditional to recent trends and the application of newly developed technologies, for strengthening the systemic approaches and providing future directions for enhancing the robustness of microbial cell factories to speed up the production of biomolecules for commercial purposes.

Biodegradable PEG-PCL Nanoparticles for Co-delivery of MUC1 Inhibitor and Doxorubicin for the Confinement of Triple-Negative Breast Cancer.

Combating triple-negative breast cancer (TNBC) is still a problem, despite the development of numerous drug delivery approaches. Mucin1 (MUC1), a glycoprotein linked to chemo-resistance and progressive malignancy, is unregulated in TNBC. GO-201, a MUC1 peptide inhibitor that impairs MUC1 activity, promotes necrotic cell death by binding to the MUC1-C unit. The current study deals with the synthesis and development of a novel nano-formulation (DM-PEG-PCL NPs) comprising of polyethylene glycol-polycaprolactone (PEG-PCL) polymer loaded with MUC1 inhibitor and an effective anticancer drug, doxorubicin (DOX). The DOX and MUC1 loaded nanoparticles were fully characterized, and their different physicochemical properties, viz. size, shape, surface charge, entrapment efficiencies, release behavior, etc., were determined. With IC50 values of 5.8 and 2.4 nm on breast cancer cell lines, accordingly, and a combination index (CI) of < 1.0, DM-PEG-PCL NPs displayed enhanced toxicity towards breast cancer cells (MCF-7 and MDA-MB-231) than DOX-PEG-PCL and MUC1i-PEG-PCL nanoparticles. Fluorescence microscopy analysis revealed DOX localization in the nucleus and MUC1 inhibitor in the mitochondria. Further, DM-PEG-PCL NPs treated breast cancer cells showed increased mitochondrial damage with enhancement in caspase-3 expression and reduction in Bcl-2 expression.In vivo evaluation using Ehrlich Ascites Carcinoma bearing mice explicitly stated that DM-PEG-PCL NPs therapy minimized tumor growth relative to control treatment. Further, acute toxicity studies did not reveal any adverse effects on organs and their functions, as no mortalities were observed. The current research reports for the first time the synergistic approach of combination entrapment of a clinical chemotherapeutic (DOX) and an anticancer peptide (MUC1 inhibitor) encased in a diblock PEG-PCL copolymer. Incorporating both DOX and MUC1 inhibitors in PEG-PCL NPs in the designed nanoformulation has provided chances and insights for treating triple-negative breast tumors. Our controlled delivery technology is biodegradable, non-toxic, and anti-multidrug-resistant. In addition, this tailored smart nanoformulation has been particularly effective in the therapy of triple-negative breast cancer. Supplementary Information: The online version contains supplementary material available at 10.1007/s10924-022-02654-4.

Immunotherapeutics in lung cancers: from mechanistic insight to clinical implications and synergistic perspectives.

BACKGROUND: Lung cancer is one of the highly lethal forms of cancer whose incidence has worldwide rapidly increased over the past few decades. About 80-85% of all lung cancer cases constitute non-small cell lung cancer (NSCLC), with adenocarcinoma, squamous cell carcinoma and large cell carcinoma as the main subtypes. Immune checkpoint inhibitors have led to significant advances in the treatment of a variety of solid tumors, significantly improving cancer patient survival rates. METHODS AND RESULTS: The cytotoxic drugs in combination with anti-PD-(L)1 antibodies is a new method that aims to reduce the activation of immunosuppressive and cancer cell prosurvival responses while also improving direct cancer cell death. The most commonly utilized immune checkpoint inhibitors for patients with non-small cell lung cancer are monoclonal antibodies (Atezolizumab, Cemiplimab, Ipilimumab, Pembrolizumab etc.) against PD-1, PD-L1, and CTLA-4. Among them, Atezolizumab (TECENTRIQ) and Cemiplimab (Libtayo) are engineered monoclonal anti programmed death ligand 1 (PD-L1) antibodies that inhibit binding of PD-L1 to PD-1 and B7.1. As a result, T-cell proliferation and cytokine synthesis are inhibited leading to restoring the immune homeostasis to fight cancer cells. CONCLUSIONS: In this review article, the path leading to the introduction of immunotherapeutic options in lung cancer treatment is described, with analyzing the benefits and shortages of the current immunotherapeutic drugs. In addition, possibilities to co-administer immunotherapeutic agents with standard cancer treatment modalities are also considered.

The exploitation of enzyme-based cancer immunotherapy.

Cancer immunotherapy utilizes the immune system and its wide-ranging components to deliver anti-tumor responses. In immune escape mechanisms, tumor microenvironment-associated soluble factors and cell surface-bound molecules are mainly accountable for the dysfunctional activity of tumor-specific CD8+ T cells, natural killer (NK) cells, tumor associated macrophages (TAMs) and stromal cells. The myeloid-derived suppressor cells (MDSCs) and Foxp3+ regulatory T cells (Tregs), are also key tumor-promoting immune cells. These potent immunosuppressive networks avert tumor rejection at various stages, affecting immunotherapies' outcomes. Numerous clinical trials have elucidated that disruption of immunosuppression could be achieved via checkpoint inhibitors. Another approach utilizes enzymes that can restore the body's potential to counter cancer by triggering the immune system inhibited by the tumor microenvironment. These immunotherapeutic enzymes can catalyze an immunostimulatory signal and modulate the tumor microenvironment via effector molecules. Herein, we have discussed the immuno-metabolic roles of various enzymes like ATP-dephosphorylating ectoenzymes, inducible Nitric Oxide Synthase, phenylamine, tryptophan, and arginine catabolizing enzymes in cancer immunotherapy. Understanding the detailed molecular mechanisms of the enzymes involved in modulating the tumor microenvironment may help find new opportunities for cancer therapeutics.

Correction: Dhatwalia et al. Rubus ellipticus Sm. Fruit Extract Mediated Zinc Oxide Nanoparticles: A Green Approach for Dye Degradation and Biomedical Applications. Materials 2022, 15, 3470.

In the original publication [...].

Onosma L. as a source of anticancer agents: phytochemistry to mechanistic insight.

Onosma (O.) is a genus of perennial flowering plants in the family Boraginaceae with approximately 250 species widely dispersed in temperate, tropical, and subtropical areas. It is traditionally used to treat rheumatism, fever, asthma, stomach irritation, and inflammatory ailments. The bioactive constituents present in the genus O. include benzoquinones, naphthazarins, alkaloids, phenolic, naphthoquinones, and flavonoids whereas shikonins and onosmins are the most significant. The review compiled contemporary research on O. L., including its distribution, morphology, traditional applications, phytochemistry, ethnopharmacology, and toxicology. This review also highlights a few critical challenges and possible future directions for O. L. research. Modern research has demonstrated a wide range of pharmacological effects of different species of O. L., including anti-diabetic, anticancer, anti-inflammatory, and cardiovascular protective. However, the studies on the O. genus are still not fully explored, therefore, researchers need to discover novel products with their toxicity studies, molecular mechanism, and associated side effects. Future exploration of potent constituents from this genus and clinical trials are required to explore its pharmacological importance.

The Colloquy between Microbiota and the Immune System in Colon Cancer: Repercussions on the Cancer Therapy.

Colorectal cancer is the second leading cause of cancer deaths worldwide and has engrossed researchers' attention toward its detection and prevention at early stages. Primarily associated with genetic and environmental risk factors, the disease has also shown its emergence due to dysbiosis in microbiota. The microbiota not only plays a role in modulating the metabolisms of metastatic tissue but also has a keen role in cancer therapy. The immune cells are responsible for secreting various chemokines and cytokines, and activating pattern recognition receptors by different microbes can lead to the trail by which these cells regulate cancer. Furthermore, mixed immune reactions involving NK cells, tumor-associated macrophages, and lymphocytes have shown their connection with the microbial counterpart of the disease. The microbes like Bacteroides fragilis, Fusobacterium nucleatum, and Enterococcus faecalis and their metabolites have engendered inflammatory reactions in the tumor microenvironment. Hence the interplay between immune cells and various microbes is utilized to study the changing metastasis stage. Targeting either immune cells or microbiota could not serve as a key to tackling this deadly disorder. However, harnessing their complementation towards the disease can be a powerful weapon for developing therapy and diagnostic/prognostic markers. In this review, we have discussed various immune reactions and microbiome interplay in CRC, intending to evaluate the effectiveness of chemotherapy and immunotherapy and their parallel relationship.