Targeting Neoantigens in Cancer: Possibilities and Opportunities in Breast Cancer.

As one of the most prevalent forms of cancer worldwide, breast cancer has garnered significant attention within the clinical research setting. While traditional treatment employs a multidisciplinary approach including a variety of therapies such as chemotherapy, hormone therapy, and even surgery, researchers have since directed their attention to the budding role of neoantigens. Neoantigens are defined as tumor-specific antigens that result from a multitude of genetic alterations, the most prevalent of which is the single nucleotide variant. As a result of their foreign nature, neoantigens elicit immune responses upon presentation by Major Histocompatibility Complexes I and II followed by recognition by T cell receptors. Previously, researchers have been able to utilize these immunogenic properties and manufacture neoantigen-specific T-cells and neoantigen vaccines. Within the context of breast cancer, biomarkers such as tumor protein 53 (TP53), Survivin, Partner and Localizer of BRCA2 (PALB2), and protein tyrosine phosphatase receptor T (PTPRT) display exceeding potential to serve as neoantigens. However, despite their seemingly limitless potential, neoantigens must overcome various obstacles if they are to be fairly distributed to patients. For instance, a prolonged period between the identification of a neoantigen and the dispersal of treatment poses a serious risk within the context of breast cancer. Regardless of these current obstacles, it appears highly promising that future research into neoantigens will make an everlasting impact on the health outcomes within the realm of breast cancer. The purpose of this literature review is to comprehensively discuss the etiology of various forms of breast cancer and current treatment modalities followed by the significance of neoantigens in cancer therapeutics and their application to breast cancer. Further, we have discussed the limitations, future directions, and the role of transcriptomics in neoantigen identification and personalized medicine. The concepts discussed in the original and review articles were included in this review article.

Targeting Neoantigens in Pancreatic Ductal Adenocarcinoma.

Pancreatic ductal adenocarcinoma (PDAC) is the most common type of pancreatic cancer and is currently the third leading cause of cancer-related death in the United States after lung and colon cancer. PDAC is estimated to be the second leading cause of cancer-related death by 2030. The diagnosis at a late stage is the underlying cause for higher mortality and poor prognosis after surgery. Treatment resistance to chemotherapy and immunotherapy results in recurrence after surgery and poor prognosis. Neoantigen burden and CD8+ T-cell infiltration are associated with clinical outcomes in PDAC and paucity of neoantigen-reactive tumor-infiltrating lymphocytes may be the underlying cause for treatment resistance for immunotherapy. This suggests a need to identify additional neoantigens and therapies targeting these neoantigens to improve clinical outcomes in PDAC. In this review, we focus on describing the pathophysiology, current treatment strategies, and treatment resistance in PDAC followed by the need to target neoantigens in PDAC.

Modulation of Inflammatory Response by Electromagnetic Field Stimulation in Traumatic Brain Injury in Yucatan Swine.

Traumatic brain injury is a leading cause of disability and death worldwide and represents a high economic burden for families and national health systems. After mechanical impact to the head, the first stage of the damage comprising edema, physical damage, and cell loss gives rise to a second phase characterized by glial activation, increased oxidative stress and excitotoxicity, mitochondrial damage, and exacerbated neuroinflammatory state, among other molecular calamities. Inflammation strongly influences the molecular events involved in the pathogenesis of TBI. Therefore, several components of the inflammatory cascade have been targeted in experimental therapies. Application of Electromagnetic Field (EMF) stimulation has been found to be effective in some inflammatory conditions. However, its effect in the neuronal recovery after TBI is not known. In this pilot study, Yucatan miniswine were subjected to TBI using controlled cortical impact approach. EMF stimulation via a helmet was applied immediately or two days after mechanical impact. Three weeks later, inflammatory markers were assessed in the brain tissues of injured and contralateral non-injured areas of control and EMF-treated animals by histomorphometry, immunohistochemistry, RT-qPCR, Western blot, and ELISA. Our results revealed that EMF stimulation induced beneficial effect with the preservation of neuronal tissue morphology as well as the reduction of inflammatory markers at the transcriptional and translational levels. Immediate EMF application showed better resolution of inflammation. Although further studies are warranted, our findings contribute to the notion that EMF stimulation could be an effective therapeutic approach in TBI patients.

miRNA profiling of esophageal adenocarcinoma using transcriptome analysis.

Esophageal adenocarcinoma (EAC) occurs following a series of histological changes through epithelial-mesenchymal transition (EMT). A variable expression of normal and aberrant genes in the tissue can contribute to the development of EAC through the activation or inhibition of critical molecular signaling pathways. Gene expression is regulated by various regulatory factors, including transcription factors and microRNAs (miRs). The exact profile of miRs associated with the pathogenesis of EAC is largely unknown, though some candidate miRNAs have been reported in the literature. To identify the unique miR profile associated with EAC, we compared normal esophageal tissue to EAC tissue using bulk RNA sequencing. RNA sequence data was verified using qPCR of 18 selected genes. Fourteen were confirmed as being upregulated, which include CDH11, PCOLCE, SULF1, GJA4, LUM, CDH6, GNA12, F2RL2, CTSZ, TYROBP, and KDELR3 as well as the downregulation of UGT1A1. We then conducted Ingenuity Pathway Analysis (IPA) to analyze for novel miR-gene relationships through Causal Network Analysis and Upstream Regulator Analysis. We identified 46 miRs that were aberrantly expressed in EAC compared to control tissues. In EAC tissues, seven miRs were associated with activated networks, while 39 miRs were associated with inhibited networks. The miR-gene relationships identified provide novel insights into potentially oncogenic molecular pathways and genes associated with carcinogenesis in esophageal tissue. Our results revealed a distinct miR profile associated with dysregulated genes. The miRs and genes identified in this study may be used in the future as biomarkers and serve as potential therapeutic targets in EAC.

Adverse Hematological Effects of COVID-19 Vaccination and Pathomechanisms of Low Acquired Immunity in Patients with Hematological Malignancies.

The SARS-CoV-2 virus and the COVID-19 pandemic have spread across the world and severely impacted patients living with hematological conditions. Immunocompromised patients experience rapidly progressing symptoms following COVID-19 infection and are at high risk of death. In efforts to protect the vulnerable population, vaccination efforts have increased exponentially in the past 2 years. Although COVID-19 vaccination is safe and effective, mild to moderate side effects such as headache, fatigue, and soreness at the injection site have been reported. In addition, there are reports of rare side effects, including anaphylaxis, thrombosis with thrombocytopenia syndrome, Guillain-Barré Syndrome, myocarditis, and pericarditis after vaccination. Further, hematological abnormalities and a very low and transient response in patients with hematological conditions after vaccination raise concerns. The objective of this review is to first briefly discuss the hematological adverse effects associated with COVID-19 infection in general populations followed by critically analyzing the side effects and pathomechanisms of COVID-19 vaccination in immunocompromised patients with hematological and solid malignancies. We reviewed the published literature, with a focus on hematological abnormalities associated with COVID-19 infection followed by the hematological side effects of COVID-19 vaccination, and the mechanisms by which complications can occur. We extend this discussion to include the viability of vaccination efforts within immune-compromised patients. The primary aim is to provide clinicians with critical hematologic information on COVID-19 vaccination so that they can make informed decisions on how to protect their at-risk patients. The secondary goal is to clarify the adverse hematological effects associated with infection and vaccination within the general population to support continued vaccination within this group. There is a clear need to protect patients with hematological conditions from infection and modulate vaccine programs and procedures for these patients.

Mitochondrial Metabolism in Pancreatic Ductal Adenocarcinoma: From Mechanism-Based Perspectives to Therapy.

Pancreatic ductal adenocarcinoma (PDAC), the fourteenth most common malignancy, is a major contributor to cancer-related death with the utmost case fatality rate among all malignancies. Functional mitochondria, regardless of their complex ecosystem relative to normal cells, are essential in PDAC progression. Tumor cells' potential to produce ATP as energy, despite retaining the redox potential optimum, and allocating materials for biosynthetic activities that are crucial for cell growth, survival, and proliferation, are assisted by mitochondria. The polyclonal tumor cells with different metabolic profiles may add to carcinogenesis through inter-metabolic coupling. Cancer cells frequently possess alterations in the mitochondrial genome, although they do not hinder metabolism; alternatively, they change bioenergetics. This can further impart retrograde signaling, educate cell signaling, epigenetic modifications, chromatin structures, and transcription machinery, and ultimately satisfy cancer cellular and nuclear demands. To maximize the tumor microenvironment (TME), tumor cells remodel nearby stromal cells and extracellular matrix. These changes initiate polyclonality, which is crucial for growth, stress response, and metastasis. Here, we evaluate all the intrinsic and extrinsic pathways drawn by mitochondria in carcinogenesis, emphasizing the perspectives of mitochondrial metabolism in PDAC progression and treatment.

Biomarkers for Early Detection, Prognosis, and Therapeutics of Esophageal Cancers.

Esophageal cancer (EC) is the deadliest cancer worldwide, with a 92% annual mortality rate per incidence. Esophageal squamous cell carcinoma (ESCC) and esophageal adenocarcinoma (EAC) are the two major types of ECs, with EAC having one of the worst prognoses in oncology. Limited screening techniques and a lack of molecular analysis of diseased tissues have led to late-stage presentation and very low survival durations. The five-year survival rate of EC is less than 20%. Thus, early diagnosis of EC may prolong survival and improve clinical outcomes. Cellular and molecular biomarkers are used for diagnosis. At present, esophageal biopsy during upper endoscopy and histopathological analysis is the standard screening modality for both ESCC and EAC. However, this is an invasive method that fails to yield a molecular profile of the diseased compartment. To decrease the invasiveness of the procedures for diagnosis, researchers are proposing non-invasive biomarkers for early diagnosis and point-of-care screening options. Liquid biopsy involves the collection of body fluids (blood, urine, and saliva) non-invasively or with minimal invasiveness. In this review, we have critically discussed various biomarkers and specimen retrieval techniques for ESCC and EAC.

Mitochondrial Biogenesis as a Therapeutic Target for Rotator Cuff Tendon Tears.

Rotator Cuff Injuries (RCI) are highly prevalent and characterized by shoulder pain, restricted shoulder movement, and difficulty with overhead activity, radiating pain in the deltoid muscle, and atrophy of the rotator cuff muscles. Increasing age, hand dominance, smoking, hypertension, hyperlipidemia, and obesity are common risk factors. Chronic inflammation plays a critical role in the underlying pathogenesis. RCI accounts for massive healthcare expenditure costing about $15,000 per repair, and over 4.5 million physician visits per year, however, there is still no therapeutic target to improve clinical outcomes. Mitochondrial biogenesis in response to inflammatory stimuli supports increased cellular energy requirements, cell proliferation, and differentiation. This suggests that mitochondrial biogenesis may play a role in healing RCI by serving as a protective factor against free oxygen species and promoting homeostasis within the rotator cuff. There is evidence highlighting the potential therapeutic benefits of mitochondrial biogenesis in various inflammatory diseases, but no study explored the role of mitochondrial biogenesis in rotator cuff tears. Since hypercholesterolemia is a risk factor for RCI, we investigated the effects of hypercholesterolemia on the expression of PGC-1α, a marker of mitochondrial biogenesis, in rotator cuff muscle. The findings revealed an increased gene and protein expression of inflammatory mediators and PGC-1α, suggesting enhanced inflammation and increased mitochondrial biogenesis due to hypercholesterolemia. Additional studies are warranted to further investigate the chronic effect of hyperlipidemia induced RCI to elucidate the cause of insufficient mitochondrial biogenesis unable to protect the rotator cuff and the therapeutic effect of promoting mitochondrial biogenesis.

Rotator Cuff Health, Pathology, and Repair in the Perspective of Hyperlipidemia.

Rotator Cuff Injuries (RCI) are prevalent cause of shoulder pain affecting over 20% of the population in the USA. Surgical repair of the torn rotator cuff helps in relieving the pressure on the rotator cuff tendon and from symptoms, however tendon-to-bone healing after rotator cuff surgery still has a high failure rate. Hyperlipidemia has been strongly associated with RCI although the cellular and molecular mechanisms are largely unknown. The focus of this critical review is to further explore the role of hyperlipidemia in RCI and rotator cuff tissue repair to determine its implication as a risk factor for tears, repair, and retears. A literature review was conducted to elucidate the role of hyperlipidemia as an inflammatory mediator and catalyst for structural instability within the shoulder. The results from various studies were critically reviewed to summarize the relationship between hyperlipidemia and rotator cuff pathology. Hyperlipidemia induces LDL-particle entrapment within the dense regular collagen of rotator cuff tendons resulting in foam cell aggregation and macrophage recruitment. Subsequent inflammatory pathways including the JAK2/STAT3 pathway and NLRP3 inflammasome pathway led to persistent inflammation and Extracellular Matrix (ECM) degradation within the rotator cuff. While arthroscopic repair remains the most common treatment modality, nonsurgical treatment including statins, vitamin D, and targeting miRNA are also of therapeutic benefit. Hyperlipidemia interferes with arthroscopic repairs by inducing inflammation and stiffness within tendons and increases the risk of retears. Most notably, targeting underlying mechanisms influencing inflammation has large therapeutic value as a novel treatment strategy for the management of rotator cuff pathology.

Targeting the Crosstalk of Immune Response and Vascular Smooth Muscle Cells Phenotype Switch for Arteriovenous Fistula Maturation.

Plaque formation, thrombosis, and embolism are the underlying causes of acute cardiovascular events such as myocardial infarction and stroke while early thrombosis and stenosis are common pathologies for the maturation failure of arteriovenous fistula (AVF). Chronic inflammation is a common underlying pathogenesis mediated by innate and adaptive immune response involving infiltration of immune cells and secretion of pro- and anti-inflammatory cytokines. Impaired immune cell infiltration and change in vascular smooth muscle cell (VSMC) phenotype play a crucial role in the underlying pathophysiology. However, the change in the phenotype of VSMCs in a microenvironment of immune cell infiltration and increased secretion of cytokines have not been investigated. Since change in VSMC phenotype regulates vessel remodeling after intimal injury, in this study, we investigated the effect of macrophages and pro-inflammatory cytokines, IL-6, IL-1ß, and TNF-α, on the change in VSMC phenotype under in vitro conditions. We also investigated the expression of the markers of VSMC phenotypes in arteries with atherosclerotic plaques and VSMCs isolated from control arteries. We found that the inhibition of cytokine downstream signaling may mitigate the effect of cytokines on the change in VSMCs phenotype. The results of this study support that regulating or targeting immune cell infiltration and function might be a therapeutic strategy to mitigate the effects of chronic inflammation to attenuate plaque formation, early thrombosis, and stenosis, and thus enhance AVF maturation.

Heterogeneous Population of Immune cells Associated with Early Thrombosis in Arteriovenous Fistula.

End-Stage Renal Disease (ESRD) is a growing cause of morbidity and mortality in the practice of modern medicine. Advances in medicine have elongated the average life span and subsequently made chronic diseases prevalent. Hemodialysis is the main treatment that is used to treat ESRD and is a clinical procedure that is being re-imagined with novel approaches to improve patient and clinic practicality and effectiveness. Arteriovenous Fistulas (AVF) are now used in place of catheters due to their higher success and lower co-morbidities. The main drawback of AVF is the time gap that is needed from the surgical creation of AVF to its use. During this time, the AVF is susceptible to thrombosis and occlusion rendering the fistula ineffective for treatment. Immune cells play a major role in vascular pathologies and macrophages, dendritic cells, and T-regulatory cells are the main cells seen during the inflammatory and anti-inflammatory phases. However, the role of immune response and immune cells in AVF maturation is poorly understood. This study aimed to investigate the immune response and immune cell expression in femoral vessels after AVF creation in a miniswine model of AVF using immunohistochemistry and qRT-PCR. The results of this study revealed an increased expression of immune cells in AVF vessels and suggest an association of immune response with AVF creation and maturation.

Immunopathogenesis, early Detection, current therapies and prevention of plantar Fasciitis: A concise review.

Plantar fasciitis or the inflammation of the fascial lining on the plantar aspect of the foot continues to be the leading cause of heel pain for many Americans. Common causes can range from anatomical deformities such as pes planus or flat foot, biomechanical etiology such as excessive pronation of the subtalar joint, or chronic diseases such as obesity and diabetes mellitus. The pathophysiology of plantar fasciitis can be either inflammatory due to vasodilation and immune system activation or non-inflammatory involving fibroblastic hypertrophy. Worsening pain of the inferior and medial heel after periods of prolonged rest and late in the day after hours of ambulation and weight-bearing activities is the most common symptom of plantar fasciitis. Common treatments for plantar fasciitis include plantar fascia stretching, physical therapy, orthotics, corticosteroid injections, and even surgery. Despite these treatment strategies, fasciitis remains a clinical problem and better treatment modalities are warranted. Late diagnosis is a common issue for prolonged and equivocal treatment and early diagnostic measures might be beneficial. In this concise review, we discussed the etiology, immunopathogenesis, current treatments of plantar fasciitis and potentially preventative measures prior to the onset of chronic treatment resistant condition.

Innate and adaptive immune cells associate with arteriovenous fistula maturation and failure.

Creation of arteriovenous fistula (AVF) causes local injury, resulting in immune response of the body and infiltration of immune cells. Acute inflammation is favorable to control inflammation and proceed AVF toward maturation while chronic inflammation in AVF leads to AVF maturation failure. Chronic inflammation in AVF is due to chronic infiltration of immune cells and secretion of inflammatory cytokines. A balance between proinflammatory and anti-inflammatory response is a must for AVF maturation and an overwhelmed proinflammatory infiltrate causes chronic inflammation and AVF failure. As immune cell infiltration plays a critical role in maturation and failure of AVF, it is important to investigate the role of immune cells as well as their density in early and late phase of AVF maturation. The role of inflammation has been discussed in the literature and this review article focuses on the role of pro- and anti-inflammatory immune cells, including macrophages, dendritic cells (DCs), T-cells, and T-regulatory (Treg) cells in AVF maturation and maturation failure.

Counteractive Effects of IL-33 and IL-37 on Inflammation in Osteoarthritis.

Osteoarthritis (OA) is a chronic inflammatory disease where pro-inflammatory cytokines, damage-associated molecular patterns (DAMPs), and macrophages play a crucial role. However, the interactive role of these mediators, the exact cause precipitating OA and definitive treatment for OA are not known yet. Moreover, the interactive role of interleukin (IL)-33 and IL-37 with other factors in the pathogenesis of OA has not been discussed elaborately. In this study, we analyzed the expression of IL-33 and IL-37 in human OA knee and hip joint cartilage tissues. The effect of increased DAMPs, IL-33, and IL-37 on IL-6, tumor necrosis factor (TNF)-α, toll-like receptors (TLRs), and matrix metalloproteinases (MMPs) expression was delineated using human normal and osteoarthritic chondrocytes. The effect of anti-inflammatory cytokine IL-37 on various mediators of inflammation in the presence of IL-33, rHMGB-1, and LPS was investigated to delineate the effects of IL-37. Further, the effects of blocking IL-33 downstream signaling and the effects of IL-33 and IL-37 on macrophage polarization were assessed along with examining the macrophage phenotypes in human OA cartilage tissues. The results of this study revealed increased expression of IL-33 in OA cartilage and that IL-33 increases IL-6, TNF-α, TLRs, and MMPs expression and favors phenotypic conversion towards the M1 phenotype, while IL-37 and blocking IL-33 receptor ST2 have opposite effects. Overall, the results suggest that blocking IL-33 and increasing IL-37 act synergistically to attenuate inflammation and might serve as potential therapeutics in OA.

Targets of immunotherapy for hepatocellular carcinoma: An update.

Hepatocellular carcinoma, the most common primary liver cancer, in an immunogenic tumor with a poor prognosis because these tumors are diagnosed at late stages. Although, surgical resection, ablation, liver transplant, and locoregional therapies are available for early stages; however, there are yet no effective treatment for advanced and recurrent tumors. Immune checkpoint inhibitor therapy and adoptive cell transfer therapy has gained the popularity with some positive results because these therapies overcome anergy and systemic immune suppression. However, still there is a lack of an effective treatment and thus there is an unmet need of a novel treatment. At present, the focus of the research is on oncolytic viral therapy and combination therapy where therapies including radiotherapy, immune checkpoint therapy, adoptive cell transfer therapy, and vaccines are combined to get an additive or synergistic effect enhancing the immune response of the liver with a cytotoxic effect on tumor cells. This review discusses the recent key development, the basis of drug resistance, immune evasion, immune tolerance, the available therapies based on stage of the tumor, and the ongoing clinical trials on immune checkpoint inhibitor therapy, adoptive cell transfer therapy, oncolytic viral vaccine therapy, and combination therapy.

Diagnostic yield of calcofluor white in the identification of Candida albicans in oral squamous cell carcinoma.

Background: Although oral cancer is multifactorial in origin only few had evaluated the diagnostic parameters for candidal infection in oral squamous cell carcinoma (OSCC). Aims: To compare and assess the accuracy of Calcofluor White (CFW) to that of conventional staining methods to identify the presence of candidal infection in OSCC. Methods: Archival collections of 43 OSCC were retrieved for this investigation. Standard staining protocol was followed for the index test (CFW) and reference standard (Periodic Acid Schiff). Two examiners were blinded for either one of the staining techniques. Diagnostic test evaluation and Kappa statistic was calculated using MedCalc software. Results: The study comprised 37 males, six females, and their mean age at the time of presentation was 51 (range 23 to 75 years). The sensitivity and specificity of CFW was 75.8% (CI 57.7 to 88.9%) and 10.0% (CI 0.2 to 44.5%). While the positive predictive and negative predictive values were 63.1% (CI - 50.6-74.0%) and 67.0% (CI - 49.2-81.0%). Conclusion: Our results show minimal agreement with PAS with a Kappa score of 0.148 (95% CI = 0.39 to 0.09). Overall detection rate was similar for both the index test and reference standard although there was considerable number of intermediate test results. Sensitivity of CFW was comparable to that of earlier studies but specificity was low and the degree of concordance was 60.4%. Although CFW staining can come with high false positive they are a useful test for ruling out candida infection when the test result is negative.

IL-33, IL-37, and Vitamin D Interaction Mediate Immunomodulation of Inflammation in Degenerating Cartilage.

Chronic joint inflammation due to increased secretion of pro-inflammatory cytokines, the accumulation of inflammatory immune cells (mainly macrophages), and vitamin D deficiency leads to cartilage degeneration and the development of osteoarthritis (OA). This study investigated the effect of vitamin D status on the expression of mediators of inflammation including interleukin (IL)-33, IL-37, IL-6, tumor necrosis factor (TNF)-α, toll-like receptors (TLRs), damage-associated molecular patterns (DAMPs), and matrix metalloproteinases (MMPs) in degenerating the cartilage of hyperlipidemic microswine. Additionally, in vitro studies with normal human chondrocytes were conducted to investigate the effect of calcitriol on the expression of IL-33, IL-37, IL-6, TNF-α, TLRs, DAMPs, and MMPs. We also studied the effects of calcitriol on macrophage polarization using THP-1 cells. The results of this study revealed that vitamin D deficiency is associated with an increased expression of IL-33, IL-37, IL-6, TNF-α, TLRs, DAMPs, and MMPs, while vitamin D supplementation is associated with a decreased expression of the former. Additionally, vitamin D deficiency is associated with increased M1, while vitamin D-supplemented microswine cartilage showed increased M2 macrophages. It was also revealed that calcitriol favors M2 macrophage polarization. Taken together, the results of this study suggest that modulating expression of IL-33, IL-6, TNF-α, TLRs, DAMPs, and MMPs with vitamin D supplementation may serve as a novel therapeutic to attenuate inflammation and cartilage degeneration in osteoarthritis.

The Role of Microbiota in the Pathogenesis of Esophageal Adenocarcinoma.

Esophageal adenocarcinoma (EAC) is associated with poor overall five-year survival. The incidence of esophageal cancer is on the rise, especially in Western societies, and the pathophysiologic mechanisms by which EAC develops are of extreme interest. Several studies have proposed that the esophageal microbiome may play an important role in the pathophysiology of EAC, as well as its precursors-gastroesophageal reflux disease (GERD) and Barrett's esophagus (BE). Gastrointestinal microbiomes altered by inflammatory states have been shown to mediate tumorigenesis directly and are now being considered as novel targets for both cancer treatment and prevention. Elucidating molecular mechanisms through which the esophageal microbiome potentiates the development of GERD, BE, and EAC will provide a foundation on which new therapeutic targets can be developed. This review summarizes current findings that elucidate the molecular mechanisms by which microbiota promote the pathogenesis of GERD, BE, and EAC, revealing potential directions for additional research on the microbiome-mediated pathophysiology of EAC.

Discerning the promising binding sites of S100/calgranulins and their therapeutic potential in atherosclerosis.

INTRODUCTION: Atherosclerosis is a chronic inflammatory disease in which the members of S100 family proteins (calgranulins) bind with their receptors, particularly receptor for advanced glycation end products (RAGE) and toll-like receptor-4 (TLR-4) and play a key role in the pathogenesis and progression of disease. Thus, these proteins could be considered as potential biomarkers and therapeutic targets in the treatment of atherosclerotic inflammation. AREAS COVERED: This review summarizes the pathology of S100A8, S100A9, and S100A12 in the development of atherosclerosis and reveals key structural features of these proteins which are potentially critical in their pathological effects. This article focuses on the translational significance of antagonizing these proteins by using small molecules in patent literature, clinical and preclinical studies and also discusses future approaches that could be employed to block these proteins in the treatment of atherosclerosis. EXPERT OPINION: Based on the critical role of S100/calgranulins in the regulation of atherosclerosis, these proteins are potential targets to develop better therapeutic options in the treatment of inflammatory diseases. However, further research is still needed to clarify their exact molecular mechanism by analyzing their detailed structural features that can expedite future research to develop novel therapeutics against these proteins to treat atherosclerotic inflammation.