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Aim: To obtain a deeper understanding of peoples' experiences of cancer treatments with immune checkpoint inhibitors (ICIs). Background: ICIs are transforming survival outcomes for many with certain advanced cancers. Given the possibility of unique immune‐related adverse events (irAEs), understanding treatment experiences is crucial to identify support needs and provide safe and effective person‐centred care. Design: A systematic review of qualitative research and thematic synthesis. To report this review, the Preferred Reporting Items for Systematic Analysis and Meta Analysis (PRISMA) checklist and Enhancing Transparency in Reporting the Synthesis of Qualitative Research (ENTREQ) guidance have been used. Data Sources: MEDLINE, EMBASE, PsycINFO, CINAHL and Web of Science databases were searched in January 2022 for eligible studies published in English from database inception. Review Methods: Two reviewers independently screened records, identified papers for inclusion and appraised methodological quality using the Critical Appraisal Skills Programme checklist. Themes were developed using thematic synthesis. Results: Eighteen papers were included and three analytical themes developed: immune checkpoint inhibitor treatment decision‐making; the experience and impact of immune checkpoint inhibitor treatments; and appraising and responding to irAEs. Conclusion: The synthesis renders visible individuals' unmet information, psychological and practical support needs. It identifies shortcomings in immune checkpoint inhibitor treatment decision‐making processes and highlights the need for healthcare professionals to recognise and sensitively handle individuals' treatment expectations. Individuals' understandings of and responses to irAEs are also illustrated, and attention drawn to patients' concerns about healthcare professionals' checkpoint inhibitor and irAEs knowledge. Implications for Patient Care: To sensitively manage treatment expectations and uncertainties, and optimise health outcomes, there are distinct points in treatment trajectories where care and support might require adapting and enhancing. Impact: This review addresses people's experiences of immune checkpoint inhibitor treatments. The core findings reveal unmet information, psychological and practical support needs. Insights derived from this review will enhance individuals' experiences and outcomes and healthcare professionals' practice. Patient or Public Contribution: No patient or public involvement. [ABSTRACT FROM AUTHOR]

Simple Summary: Proton pump inhibitors are frequently used in cancer patients to alleviate some symptoms, epigastric pain or heartburn. However, acid suppression decreases the absorption of some oral-targeted anticancer treatments (tyrosine kinase inhibitors, CDK4/6 inhibitors) and induces changes in the gut microbiome. Recent data are showing that these interactions have important clinical impacts and medical oncologists and patients must be aware of these possible interactions. Multikinase inhibitors (MKIs), and particularly tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (CPIs), are currently some of the major breakthroughs in cancer treatment. Proton pump inhibitors (PPIs) revolutionised the treatment of acid-related diseases, but are frequently overused for epigastric pain or heartburn. However, long-term acid suppression from using PPIs may lead to safety concerns, and could have a greater impact in cancer patients undergoing therapy, like bone fractures, renal toxicities, enteric infections, and micronutrient deficiencies (iron and magnesium). Moreover, acid suppression may also affect the pharmacokinetics of drugs (at least during acid suppression) and decrease the absorption of many molecularly-targeted anticancer therapies, which are mostly weak bases with pH-dependent absorption. This type of drug-drug interaction may have detrimental effects on efficacy, with major clinical impacts described for some orally administrated targeted therapies (erlotinib, gefitinib, pazopanib, palbociclib), and conflicting results with many others, including capecitabine. Furthermore, the long-term use of PPIs results in severe alterations to the gut microbiome and recent retrospective analyses have shown that the benefit of using CPIs was suppressed in patients treated with PPIs. These very expensive drugs are of great importance because of their efficacy. As the use of PPIs is not essential, we must apply the precautionary principle. All these data should encourage medical oncologists to refrain from prescribing PPIs, explaining to patients the risks of interaction in order to prevent inappropriate prescription by another physician. [ABSTRACT FROM AUTHOR]

Simple Summary: Immunotherapy targeting immune checkpoints and stromal cells in the tumor microenvironment is currently one of the most promising directions for tumor therapy. Ongoing studies suggest that CD73 plays an important role in the tumor immune process in certain tumors, however, the exact mechanism is unknown. We aim to fully reveal the prognostic value of CD73 in pan-cancer and its role in tumor immunity through large-scale single-cell and bulk sequencing analysis. We found that high CD73 expression was significantly associated with poor prognosis in many tumors. It is also strongly associated with immune scores, stromal cell infiltration, and immune-related pathways. CD73 can regulate the biological behavior of immune cells in the tumor microenvironment, especially macrophages and T cells. Immunotherapy targeting CD73 has obvious effects, and CD73 may shine as a new immune checkpoint in future tumor immunotherapy. CD73 is essential in promoting tumor growth by prohibiting anti-tumor immunity in many cancer types. While the mechanism remains largely unknown, our paper comprehensively confirmed the onco-immunological characteristics of CD73 in the tumor microenvironment (TME) of pan-cancer. This paper explored the expression pattern, mutational profile, prognostic value, tumor immune infiltration, and response to immunotherapy of CD73 in a continuous cohort of cancers through various computational tools. The co-expression of CD73 on cancer cells, immune cells, and stromal cells in the TME was also detected. Especially, we examined the correlation between CD73 and CD8+ (a marker of T cell), CD68+ (a marker of macrophage), and CD163+ (a marker of M2 macrophage) cells using multiplex immunofluorescence staining of tissue microarrays. CD73 expression is significantly associated with a patient's prognosis and could be a promising predictor of these cancers. High CD73 levels are strongly linked to immune infiltrations, neoantigens, and immune checkpoint expression in the TME. In particular, enrichment signaling pathway analysis demonstrated that CD73 was obviously related to activation pathways of immune cells, including T cells, macrophages, and cancer-associated fibroblasts (CAFs). Meanwhile, single-cell sequencing algorithms found that CD73 is predominantly co-expressed on cancer cells, CAFs, M2 macrophages, and T cells in several cancers. In addition, we explored the cellular communication among 14 cell types in glioblastoma (GBM) based on CD73 expression. Based on the expression of CD73 as well as macrophage and T cell markers, we predicted the methylation and enrichment pathways of these markers in pan-cancer. Furthermore, a lot of therapeutic molecules sensitive to these markers were predicted. Finally, potential anticancer inhibitors, immunotherapies, and gene therapy responses targeting CD73 were identified from a series of immunotherapy cohorts. CD73 is closely linked to clinical prognosis and immune infiltration in many cancers. Targeting CD73-dependent signaling pathways may be a promising therapeutic strategy for future tumor immunotherapy. [ABSTRACT FROM AUTHOR]

Simple Summary: Although immunotherapy has improved the treatment and outcome of cancer patients, there are still limitations to face because most patients cannot receive lasting benefits. We believe it is urgent to discover new potential biomarkers and therapeutic targets for investigating personalized and less invasive anticancer treatments. In the present paper, we highlight: (i) the impact of ubiquitination and its reverse, de-ubiquitination, in orchestrating the immune response of the tumor microenvironment; (ii) selected clinical trials, which provide information on combination cancer immunotherapy and new immunomodulatory targets; (iii) current challenges in immunotherapy, including imaging technologies and ROS-based immunotherapies, as well as immunotherapy side effects. Finally, the major outstanding questions in cancer immunotherapy are also presented, and directions for future research are described. Immunotherapy is a cancer treatment that exploits the capacity of the body's immune system to prevent, control, and remove cancer. Immunotherapy has revolutionized cancer treatment and significantly improved patient outcomes for several tumor types. However, most patients have not benefited from such therapies yet. Within the field of cancer immunotherapy, an expansion of the combination strategy that targets independent cellular pathways that can work synergistically is predicted. Here, we review some consequences of tumor cell death and increased immune system engagement in the modulation of oxidative stress and ubiquitin ligase pathways. We also indicate combinations of cancer immunotherapies and immunomodulatory targets. Additionally, we discuss imaging techniques, which are crucial for monitoring tumor responses during treatment and the immunotherapy side effects. Finally, the major outstanding questions are also presented, and directions for future research are described. [ABSTRACT FROM AUTHOR]

Simple Summary: The tumor microenvironment (TME) has a vital role in cancer development, progression, and metastasis. It can shape immune infiltration and activation within tumors, including the role of macrophages, tumor effector cells, and the uptake of therapeutic drugs or nanoparticles. In this manuscript, we report on the feasibility and preliminary efficacy of administering E. coli phagelysate (EcPHL) as a primer to modify the TME, including the enhanced uptake of magnetic nanoparticles (mNP) by tumor-associated macrophages (TAM) and tumor cells. The tumor microenvironment (TME), where cancer cells reside, plays a crucial role in cancer progression and metastasis. It maintains an immunosuppressive state in many tumors and regulates the differentiation of precursor monocytes into M1 (anti-tumor)- and M2 (pro-tumor)-polarized macrophages, and greatly reduces anticancer drug and nanoparticle delivery. As a result, the effectiveness of recently developed chemo- and/or nanotechnology-mediated immune and magnetic nanoparticle hyperthermia (mNPH) therapies is inhibited significantly. One of the ways to overcome this limitation is to use E. coli phagelysate as a primer to modify the tumor microenvironment by switching tumor-associated M2 macrophages to anti-tumor M1 macrophages, and initiate the infiltration of tumor-associated macrophages (TAMs). Recently, bacteriophages and phage-induced lysed bacteria (bacterial phagelysates—BPLs) have been shown to be capable of modifying the tumor-associated environment. Phage/BPL-coated proteins tend to elicit strong anti-tumor responses from the innate immune system, prompting phagocytosis and cytokine release. It has also been reported that the microenvironments of bacteriophage- and BPL-treated tumors facilitate the conversion of M2-polarized TAMS to a more M1-polarized (tumoricidal) environment post-phage treatment. This paper demonstrates the feasibility and enhanced efficacy of combining E. coli phagelysate (EcPHL) and mNPH, a promising technology for treating cancers, in a rodent model. Specifically, we illustrate the EcPHL vaccination effect on the TME and mNP distribution in Ehrlich adenocarcinoma tumors by providing the tumor growth dynamics and histology (H&E and Prussian blue) distribution of mNP in tumor and normal tissue. [ABSTRACT FROM AUTHOR]

Simple Summary: Drugs are used to treat cancer. Most drugs available in the market are chemosynthetic drugs and have side effects on the patient during and after the treatment, in addition to cancer itself. For instance, hair loss, loss of skin color and texture, loss of energy, nausea, infertility, etc. To overcome these side effects, naturally obtained drugs from medicinal plants are preferred. Our review paper aims to encourage the study of anticancer medicinal plants by giving detailed information on thirty-three medicinal plants and parts that constitute the phytochemicals responsible for the treatment of cancer. The development of plant-based drugs could be a game changer in treating cancer as well as boosting the immune system. Cancer is a serious and significantly progressive disease. Next to cardiovascular disease, cancer has become the most common cause of mortality in the entire world. Several factors, such as environmental factors, habitual activities, genetic factors, etc., are responsible for cancer. Many cancer patients seek alternative and/or complementary treatments because of the high death rate linked with cancer and the adverse side effects of chemotherapy and radiation therapy. Traditional medicine has a long history that begins with the hunt for botanicals to heal various diseases, including cancer. In the traditional medicinal system, several plants used to treat diseases have many bioactive compounds with curative capability, thereby also helping in disease prevention. Plants also significantly contributed to the modern pharmaceutical industry throughout the world. In the present review, we have listed 33 medicinal plants with active and significant anticancer activity, as well as their anticancer compounds. This article will provide a basic set of information for researchers interested in developing a safe and nontoxic active medicinal plant-based treatment for cancer. The research will give a scientific foundation for the traditional usage of these medicinal herbs to treat cancer. [ABSTRACT FROM AUTHOR]

Simple Summary: Growing evidence indicates that blood-count-based compound scores could be used as prognostic biomarkers in cancer as reflectors of uncontrolled inflammation in the tumor microenvironment. Several markers have been developed in this regard, including the recent pan-immune-inflammation value (PIV) that incorporates the levels of blood neutrophil, monocyte, platelet, and lymphocytes. In this paper, we reviewed the association between PIV and overall survival or progression-free survival in cancer from the published studies to date. We observed that higher PIV levels were an adverse prognostic factor consistently across several clinical scenarios, including non-metastatic or metastatic disease and treatment with targeted therapy or immunotherapy. In contrast, the data were limited in patients treated with chemotherapy or patients with non-metastatic disease. The available evidence demonstrates that PIV could be a readily available biomarker for prognosis prediction in cancer. However, further research is needed to explore the promise of PIV as a prognostic biomarker in cancer. Background: Prognostic scores derived from the blood count have garnered significant interest as an indirect measure of the inflammatory pressure in cancer. The recently developed pan-immune-inflammation value (PIV), an equation including the neutrophil, platelet, monocyte, and lymphocyte levels, has been evaluated in several cohorts, although with variations in the tumor types, disease stages, cut-offs, and treatments. Therefore, we evaluated the association between survival and PIV in cancer, performing a systematic review and meta-analysis. Methods: We conducted a systematic review from the Pubmed, Medline, and Embase databases to filter the published studies until 17 May 2022. The meta-analyses were performed with the generic inverse-variance method with a random-effects model. Results: Fifteen studies encompassing 4942 patients were included. In the pooled analysis of fifteen studies, the patients with higher PIV levels had significantly increased risk of death than those with lower PIV levels (HR: 2.00, 95% CI: 1.51–2.64, p < 0.001) and increased risk of progression or death (HR: 1.80, 95% CI: 1.39–2.32, p < 0.001). Analyses were consistent across several clinical scenarios, including non-metastatic or metastatic disease, different cut-offs (500, 400, and 300), and treatment with targeted therapy or immunotherapy (p < 0.001 for each). Conclusion: The available evidence demonstrates that PIV could be a prognostic biomarker in cancer. However, further research is needed to explore the promise of PIV as a prognostic biomarker in patients with non-metastatic disease or patients treated without immunotherapy or targeted therapy. [ABSTRACT FROM AUTHOR]

In this paper, we study ultimate dynamics and derive tumor eradication conditions for the angiogenic switch model developed by Viger et al. This model describes the behavior and interactions between host (x); effector (y); tumor (z); endothelial (w) cell populations. Our approach is based on using the localization method of compact invariant sets and the LaSalle theorem. The ultimate upper bound for each cell population and ultimate lower bound for the effector cell population are found. These bounds describe a location of all bounded dynamics. We construct the domain bounded in x - and z -variables which contains the attracting set of the system. Further, we derive conditions imposed on the model parameters for the location of omega-limit sets in the plane w = 0 (the case of a localized tumor). Next, we present conditions imposed on the model and treatment parameters for the location of omega-limit sets in the plane z = 0 (the case of global tumor eradication). Various types of dynamics including the chaotic attractor and convergence dynamics are described. Numerical simulation illustrating tumor eradication theorems is fulfilled as well. [ABSTRACT FROM AUTHOR]

Background: Cancer is a complex, multiscale dynamical system, with interactions between tumor cells and non-cancerous host systems. Therapies act on this combined cancer-host system, sometimes with unexpected results. Systematic investigation of mechanistic computational models can augment traditional laboratory and clinical studies, helping identify the factors driving a treatment's success or failure. However, given the uncertainties regarding the underlying biology, these multiscale computational models can take many potential forms, in addition to encompassing high-dimensional parameter spaces. Therefore, the exploration of these models is computationally challenging. We propose that integrating two existing technologies—one to aid the construction of multiscale agent-based models, the other developed to enhance model exploration and optimization—can provide a computational means for high-throughput hypothesis testing, and eventually, optimization. Results: In this paper, we introduce a high throughput computing (HTC) framework that integrates a mechanistic 3-D multicellular simulator (PhysiCell) with an extreme-scale model exploration platform (EMEWS) to investigate high-dimensional parameter spaces. We show early results in applying PhysiCell-EMEWS to 3-D cancer immunotherapy and show insights on therapeutic failure. We describe a generalized PhysiCell-EMEWS workflow for high-throughput cancer hypothesis testing, where hundreds or thousands of mechanistic simulations are compared against data-driven error metrics to perform hypothesis optimization. Conclusions: While key notational and computational challenges remain, mechanistic agent-based models and high-throughput model exploration environments can be combined to systematically and rapidly explore key problems in cancer. These high-throughput computational experiments can improve our understanding of the underlying biology, drive future experiments, and ultimately inform clinical practice. [ABSTRACT FROM AUTHOR]

Poor drug delivery and low rates of cell proliferation are two factors associated with hypoxia that diminish the efficacy of many chemotherapeutic drugs. Since macrophages are known to migrate specifically towards, and localize within, hypoxic tumour regions, a promising resolution to these problems involves genetically engineering macrophages to perform such anti-tumour functions as inducing cell lysis and inhibiting angiogenesis. In this paper we outline a modelling approach to characterize macrophage infiltration into early avascular solid tumours, and extensions to study the interaction of these cells with macrophages already present within the tumour. We investigate the role of chemotaxis and chemokine production, and the efficacy of macrophages as vehicles for drug delivery to hypoxic tumour sites.The model is based upon a growing avascular tumour spheroid, in which volume is filled by tumour cells, macrophages and extracellular material, and tumour cell proliferation and death is regulated by nutrient diffusion. Crucially, macrophages occupy volume, and hence contribute to the volume balance and hence the size of the tumour. We also include oxygen-dependent production of macrophage chemokines, which can lead to accumulations in the hypoxic region of the tumour. We find that the macrophage chemotactic sensitivity is a key determinant of macrophage infiltration and tumour size. Although increased infiltration should be beneficial from the point of view of macrophage-based therapies, such infiltration in fact leads to increased tumour sizes.Finally, we include terms representing the induced death of tumour cells by hypoxic engineered macrophages. We demonstrate that reductions in tumour size can be achieved, but predict that a combination of therapies would be required for complete eradication. We also highlight some counter-intuitive predictions—for example, absolute and relative measures of tumour burden lead to different conclusions about prognosis. In summary, this paper illustrates how mathematical models may be used to investigate promising macrophage-based therapies. [Copyright &y& Elsevier]

Treatment of brain cancers, especially high grade gliomas (WHO stage III and IV) is slowly making progress, but not as fast as medical researchers and the patients would like. Immunotherapy offers the opportunity to allow the patient's own immune system a chance to help eliminate the cancer. Immunotherapy's strength is that it efficiently treats relatively small tumors in experimental animal models. For some patients, immunotherapy has worked for them while not showing long-term toxicity. In this paper, we will trace the history of immunotherapy for brain cancers.We will also highlight some of the possible directions that this field may be taking in the immediate future for improving this therapeutic option. [ABSTRACT FROM AUTHOR]

The last decade has seen a considerable improvement in the understanding of the biology of melanoma. Advances have come in the understanding of the importance of critical oncogenes and tumour suppressor genes, epigenetic phenomena, signalling pathways, drug resistance mechanisms, the pivotal role of the local immune system, and the importance of cell–cell and cell–matrix interactions. Many of these pathways and interactions include potentially ‘drugable’ targets. These developments have allowed the identification and/or design of a range of new, targeted therapies. Evaluation of these new drugs has brought a whole new series of challenges. These include indentification of appropriate pre-clinical models, overcoming the redundancy inbuilt in complex biological systems, identification of appropriate molecular and clinical endpoints to show that the drug is hitting the target, how to combine treatments, and new toxicities. For the first time, there is the possibility of personalised treatment for melanoma patients, based on individual host and tumour characteristics. This paper discusses the range of new drugs and targets have been identified, the outcome of clinical trials, and the directions for future advances. [ABSTRACT FROM AUTHOR]

Simple Summary: Immune modulation is considered a hallmark of cancer initiation and progression, and has offered promising opportunities for therapeutic manipulation. Multiplex immunofluorescence (mIF) technology has enabled the tumor immune microenvironment (TIME) to be studied at an increased scale, in terms of both the number of markers and the number of samples. Another benefit of mIF technology is the ability to measure not only the abundance but also the spatial location of multiple cells types within a tissue sample simultaneously, allowing for assessment of the co-localization of different types of immune markers. Thus, the use of mIF technologies have enable researchers to characterize patient, clinical, and tumor characteristics in the hope of identifying patients whom might benefit from immunotherapy treatments. In this review we outline some of the challenges and opportunities in the statistical analyses of mIF data to study the TIME. Immune modulation is considered a hallmark of cancer initiation and progression. The recent development of immunotherapies has ushered in a new era of cancer treatment. These therapeutics have led to revolutionary breakthroughs; however, the efficacy of immunotherapy has been modest and is often restricted to a subset of patients. Hence, identification of which cancer patients will benefit from immunotherapy is essential. Multiplex immunofluorescence (mIF) microscopy allows for the assessment and visualization of the tumor immune microenvironment (TIME). The data output following image and machine learning analyses for cell segmenting and phenotyping consists of the following information for each tumor sample: the number of positive cells for each marker and phenotype(s) of interest, number of total cells, percent of positive cells for each marker, and spatial locations for all measured cells. There are many challenges in the analysis of mIF data, including many tissue samples with zero positive cells or "zero-inflated" data, repeated measurements from multiple TMA cores or tissue slides per subject, and spatial analyses to determine the level of clustering and co-localization between the cell types in the TIME. In this review paper, we will discuss the challenges in the statistical analysis of mIF data and opportunities for further research. [ABSTRACT FROM AUTHOR]

Simple Summary: The clinical success in immunotherapy has been remarkable, and, at the same time, disappointing. The immune context of the tumour microenvironment has an influence on tumour initiation, response, and therapy. It is an urgent matter to explore mechanisms shaping the tumour microenvironment for further progression of immunotherapy. The immunoreceptor retinoic acid-induced gene-I (RIG-I) has emerged as a promising target molecule to activate adoptive immunity via activation of innate immunity. In this paper, we highlight basic mechanisms of RIG-I signalling in the tumour microenvironment, broadening to the most recent preclinical studies that employ RIG-I agonists. We also present an up-to-date selection of clinical trials designed to prove the antitumour role of RIG I, and that may result in improved therapeutic outcomes for cancer patients. Over the last 15 years, the ability to harness a patient's own immune system has led to significant progress in cancer therapy. For instance, immunotherapeutic strategies, including checkpoint inhibitors or adoptive cell therapy using chimeric antigen receptor T-cell (CAR-T), are specifically aimed at enhancing adaptive anti-tumour immunity. Several research groups demonstrated that adaptive anti-tumour immunity is highly sustained by innate immune responses. Host innate immunity provides the first line of defence and mediates recognition of danger signals through pattern recognition receptors (PRRs), such as cytosolic sensors of pathogen-associated molecular patterns (PAMPs) and damage-associated molecular pattern (DAMP) signals. The retinoic acid-inducible gene I (RIG-I) is a cytosolic RNA helicase, which detects viral double-strand RNA and, once activated, triggers signalling pathways, converging on the production of type I interferons, proinflammatory cytokines, and programmed cell death. Approaches aimed at activating RIG-I within cancers are being explored as novel therapeutic treatments to generate an inflammatory tumour microenvironment and to facilitate cytotoxic T-cell cross-priming and infiltration. Here, we provide an overview of studies regarding the role of RIG-I signalling in the tumour microenvironment, and the most recent preclinical studies that employ RIG-I agonists. Lastly, we present a selection of clinical trials designed to prove the antitumour role of RIG I and that may result in improved therapeutic outcomes for cancer patients. [ABSTRACT FROM AUTHOR]

Cancer is associated with higher morbidity and mortality and is the second leading cause of death in the US. Further, in some nations, cancer has overtaken heart disease as the leading cause of mortality. Identification of molecular mechanisms by which cancerous cells evade T cell-mediated cytotoxic damage has led to the modern era of immunotherapy in cancer treatment. Agents that release these immune brakes have shown activity to recover dysfunctional T cells and regress various cancer. Both cytotoxic T-lymphocyte-associated protein 4 (CTLA-4) and Programmed Death-1 (PD-1) play their role as physiologic brakes on unrestrained cytotoxic T effector function. CTLA-4 (CD 152) is a B7/CD28 family; it mediates immunosuppression by indirectly diminishing signaling through the co-stimulatory receptor CD28. Ipilimumab is the first and only FDA-approved CTLA-4 inhibitor; PD-1 is an inhibitory transmembrane protein expressed on T cells, B cells, Natural Killer cells (NKs), and Myeloid-Derived Suppressor Cells (MDSCs). Programmed Death-Ligand 1 (PD-L1) is expressed on the surface of multiple tissue types, including many tumor cells and hematopoietic cells. PD-L2 is more restricted to hematopoietic cells. Blockade of the PD-1 /PDL-1 pathway can enhance anti-tumor T cell reactivity and promotes immune control over the cancerous cells. Since the FDA approval of ipilimumab (human IgG1 k anti-CTLA-4 monoclonal antibody) in 2011, six more immune checkpoint inhibitors (ICIs) have been approved for cancer therapy. PD-1 inhibitors nivolumab, pembrolizumab, cemiplimab and PD-L1 inhibitors atezolizumab, avelumab, and durvalumab are in the current list of the approved agents in addition to ipilimumab. In this review paper, we discuss the role of each immune checkpoint inhibitor (ICI), the landmark trials which led to their FDA approval, and the strength of the evidence per National Comprehensive Cancer Network (NCCN), which is broadly utilized by medical oncologists and hematologists in their daily practice. [ABSTRACT FROM AUTHOR]