Bispecific PD1-IL2v and anti-PD-L1 break tumor immunity resistance by enhancing stem-like tumor-reactive CD8+ T cells and reprogramming macrophages.

Immunotherapies have shown remarkable, albeit tumor-selective, therapeutic benefits in the clinic. Most patients respond transiently at best, highlighting the importance of understanding mechanisms underlying resistance. Herein, we evaluated the effects of the engineered immunocytokine PD1-IL2v in a mouse model of de novo pancreatic neuroendocrine cancer that is resistant to checkpoint and other immunotherapies. PD1-IL2v utilizes anti-PD-1 as a targeting moiety fused to an immuno-stimulatory IL-2 cytokine variant (IL2v) to precisely deliver IL2v to PD-1+ T cells in the tumor microenvironment. PD1-IL2v elicited substantial infiltration by stem-like CD8+ T cells, resulting in tumor regression and enhanced survival in mice. Combining anti-PD-L1 with PD1-IL2v sustained the response phase, improving therapeutic efficacy both by reprogramming immunosuppressive tumor-associated macrophages and enhancing T cell receptor (TCR) immune repertoire diversity. These data provide a rationale for clinical trials to evaluate the combination therapy of PD1-IL2v and anti-PD-L1, particularly in immunotherapy-resistant tumors infiltrated with PD-1+ stem-like T cells.

Natural killer cells and engagers: Powerful weapons against cancer.

Natural killer (NK) cells are innate immune effectors whose functions rely on receptors binding cytokines, recognizing self-molecules, or detecting danger signals expressed by virus-infected or tumor cells. The potent cytotoxic potential makes NK cells promising candidates for cancer immunotherapy. To enhance their activity strategies include cytokine administration, blocking of immune checkpoints, and designing of antibody-based NK cell engagers (NKCEs). NKCEs represent a cutting-edge approach to cancer therapy: they strengthen the NK-to-target cell interactions and optimize tumor killing, possibly overcoming the immunosuppressive tumor microenvironment. NK cells belong to the innate lymphoid cells (ILCs) and are categorized into different subsets also including cells with a memory-like phenotype: this complexity needs to be explored in the context of cancer immunotherapy, particularly when designing NKCEs. Two strategies to enhance NK cell activity in cancer patients can be adopted: activating patients' own NK cells versus the adoptive transfer of ex vivo activated NK cells. Furthermore, the capability of NKCEs to activate γδ T cells could have a significant synergistic effect in immunotherapy.

Regulation of innate immune system function by the microbiome: Consequences for tumor immunity and cancer immunotherapy.

Innate effector cells are immune cells endowed with host protective features and cytotoxic functions. By sensing the tissue environment, innate cells have an important role in regulating the transition from homeostasis to inflammation and the establishment of pathological states, including the onset and development of cancer. The tumor microenvironment induces molecular and functional modifications in innate cells, dampening their capability to initiate and sustain anti-tumor immune responses. Emerging studies clearly showed a contribution of the microbiota in modulating the functions of innate cells in cancer. Commensal microorganisms can not only directly interact with innate cells in the tumor microenvironment but can also exert immunomodulatory features from non-tumor sites through the release of microbial products. The microbiota can mediate the priming of innate cells at mucosal tissues and determine the strength of immune responses mediated by such cells when they migrate to non-mucosal tissues, having an impact on cancer. Finally, several evidences reported a strong contribution of the microbiota in promoting innate immune responses during anti-cancer therapies leading to enhanced therapeutic efficacy. In this review, we considered the current knowledge on the role of the microbiota in shaping host innate immune responses in cancer.

Integrating immunopeptidome analysis for the design and development of cancer vaccines.

The repertoire of naturally presented peptides within the MHC (major histocompatibility complex) or HLA (human leukocyte antigens) system on the cellular surface of every mammalian cell is referred to as ligandome or immunopeptidome. This later gained momentum upon the discovery of CD8 + T cells able to recognize and kill cancer cells in an MHC-I antigen-restricted manner. Indeed, cancer immune surveillance relies on T cell recognition of MHC-I-restricted peptides, making the identification of those peptides the core for designing T cell-based cancer vaccines. Moreover, the breakthrough of antibodies targeting immune checkpoint molecules has led to a new and strong interest in discovering suitable targets for CD8 +T cells. Therapeutic cancer vaccines are designed for the artificial generation and/or stimulation of CD8 +T cells; thus, their combination with ICIs to unleash the breaks of the immune system comes as a natural consequence to enhance anti-tumor efficacy. In this context, the identification and knowledge of peptide candidates take advantage of the fast technology updates in immunopeptidome and mass spectrometric methodologies, paying the way to the rational design of vaccines for immunotherapeutic approaches. In this review, we discuss mainly the role of immunopeptidome analysis and its application for the generation of therapeutic cancer vaccines with main focus on HLA-I peptides. Here, we review cancer vaccine platforms based on two different preparation methods: pathogens (viruses and bacteria) and not (VLPs, nanoparticles, subunits vaccines) that exploit discoveries in the ligandome field to generate and/or enhance anti-tumor specific response. Finally, we discuss possible drawbacks and future challenges in the field that remain still to be addressed.

Germline mechanisms of immunotherapy toxicities in the era of genome-wide association studies.

Cancer immunotherapy has revolutionized the treatment of advanced cancers and is quickly becoming an option for early-stage disease. By reactivating the host immune system, immunotherapy harnesses patients' innate defenses to eradicate the tumor. By putatively similar mechanisms, immunotherapy can also substantially increase the risk of toxicities or immune-related adverse events (irAEs). Severe irAEs can lead to hospitalization, treatment discontinuation, lifelong immune complications, or even death. Many irAEs present with similar symptoms to heritable autoimmune diseases, suggesting that germline genetics may contribute to their onset. Recently, genome-wide association studies (GWAS) of irAEs have identified common germline associations and putative mechanisms, lending support to this hypothesis. A wide range of well-established GWAS methods can potentially be harnessed to understand the etiology of irAEs specifically and immunotherapy outcomes broadly. This review summarizes current findings regarding germline effects on immunotherapy outcomes and discusses opportunities and challenges for leveraging germline genetics to understand, predict, and treat irAEs.

Gastrointestinal mucosal toxicities from immune checkpoint inhibitors: Current understanding and future directions.

Immune checkpoint inhibitor (ICI) therapy has revolutionized the field of oncology over the past decade, leading to durable remissions in some patients but also producing a wide spectrum of treatment-limiting inflammatory toxicities that are referred to as immune-related adverse events (irAEs). Although irAEs can involve any organ system in the body, they most commonly affect the barrier tissues, including the gastrointestinal tract with colitis and enterocolitis affecting a significant fraction of patients on ICIs. We are beginning to understand the mechanisms that drive ICI colitis, with early experiments indicating a role for CD8+ resident memory T cells (TRMs) in the gut, which become activated and differentiate into cytotoxic cells in response to ICI therapy. The risk factors that define who will develop ICI colitis are not understood and substantial efforts are underway to identify potential biomarkers for risk of this and other toxicities. Optimal management of ICI colitis is also an area of active investigation. Current standard treatments are based largely on small, retrospective analyses, and while drugs like systemic glucocorticoids or the TNFα inhibitor infliximab do appear to be highly active in ICI colitis, the impact of these therapies on antitumor responses is poorly understood. As discussed in this review, future work will have to define the immune mechanisms driving ICI colitis in more detail and in comparison to antitumor responses in order to identify candidate pathways that can be targeted to improve ICI colitis without interfering in antitumor immunity. Studying these interventions will require randomized, controlled trials with both tumor and colitis endpoints, a goal that will necessitate collaboration across institutions and funding agencies. We are at a point where such collaborative trials are feasible, and have the potential to greatly improve the care of patients with ICI colitis as well as other irAEs.

Immunological mechanisms underlying clinical phenotypes and noninvasive diagnosis of immune checkpoint inhibitor-induced kidney disease.

Immune checkpoint inhibitors (ICIs) have become a mainstay of cancer therapy, with over 80 FDA-approved indications. Used in a variety of settings and in combination with each other and with traditional chemotherapies, the hyperactive immune response induced by ICIs can often lead to immune-related adverse events in bystander normal tissues such as the kidneys, lungs, and the heart. In the kidneys, this immune-related adverse event manifests as acute interstitial nephritis (ICI-AIN). In the era of widespread ICI use, it becomes vital to understand the clinical manifestations of ICI-AIN and the importance of prompt diagnosis and management of these complications. In this review, we delve into the clinical phenotypes of ICI-AIN and how they differ from traditional drug-induced AIN. We also detail what is known about the mechanistic underpinnings of ICI-AIN and the important diagnostic and therapeutic implications behind harnessing those mechanisms to further our understanding of these events and to formulate effective treatment plans to manage ICI-AIN.

Coengineering specificity, safety, and function into T cells for cancer immunotherapy.

Adoptive T-cell transfer (ACT) therapies, including of tumor infiltrating lymphocytes (TILs) and T cells gene-modified to express either a T cell receptor (TCR) or a chimeric antigen receptor (CAR), have demonstrated clinical efficacy for a proportion of patients and cancer-types. The field of ACT has been driven forward by the clinical success of CD19-CAR therapy against various advanced B-cell malignancies, including curative responses for some leukemia patients. However, relapse remains problematic, in particular for lymphoma. Moreover, for a variety of reasons, relative limited efficacy has been demonstrated for ACT of non-hematological solid tumors. Indeed, in addition to pre-infusion challenges including lymphocyte collection and manufacturing, ACT failure can be attributed to several biological processes post-transfer including, (i) inefficient tumor trafficking, infiltration, expansion and retention, (ii) chronic antigen exposure coupled with insufficient costimulation resulting in T-cell exhaustion, (iii) a range of barriers in the tumor microenvironment (TME) mediated by both tumor cells and suppressive immune infiltrate, (iv) tumor antigen heterogeneity and loss, or down-regulation of antigen presentation machinery, (v) gain of tumor intrinsic mechanisms of resistance such as to apoptosis, and (vi) various forms of toxicity and other adverse events in patients. Affinity-optimized TCRs can improve T-cell function and innovative CAR designs as well as gene-modification strategies can be used to coengineer specificity, safety, and function into T cells. Coengineering strategies can be designed not only to directly support the transferred T cells, but also to block suppressive barriers in the TME and harness endogenous innate and adaptive immunity. Here, we review a selection of the remarkable T-cell coengineering strategies, including of tools, receptors, and gene-cargo, that have been developed in recent years to augment tumor control by ACT, more and more of which are advancing to the clinic.

Diving into the mechanism of action of tumor immunotherapies with intravital imaging.

The clinical successes and tremendous hopes raised by tumor immunotherapies such as tumor-targeting monoclonal antibodies, immune checkpoint blockers, or CAR T cells demand that we better understand how these treatments precisely act in the patient body. Such a detailed knowledge is indeed essential to optimize therapeutical efficacy and maximize the number of cancer patients that could benefit from these therapies. This review aims to illustrate that intravital two-photon imaging is providing unique insights into the mode of action of tumor immunotherapies and is helping identify their critical bottlenecks in vivo. Moreover, this article discusses how spatiotemporal observations of immune cells, tumor subclones, and cytokine dynamics in the tumor microenvironment may contribute to the emergence of new concepts in anti-tumor immune responses.

Immunological approaches to HIV cure.

Combination antiretroviral therapy (ART) to treat human immunodeficiency virus (HIV) infection has proven remarkably successful - for those who can access and afford it - yet HIV infection persists indefinitely in a reservoir of cells, despite effective ART and despite host antiviral immune responses. An HIV cure is therefore the next aspirational goal and challenge, though approaches differ in their objectives - with 'functional cures' aiming for durable viral control in the absence of ART, and 'sterilizing cures' aiming for the more difficult to realize objective of complete viral eradication. Mechanisms of HIV persistence, including viral latency, anatomical sequestration, suboptimal immune functioning, reservoir replenishment, target cell-intrinsic immune resistance, and, potentially, target cell distraction of immune effectors, likely need to be overcome in order to achieve a cure. A small fraction of people living with HIV (PLWH) naturally control infection via immune-mediated mechanisms, however, providing both sound rationale and optimism that an immunological approach to cure is possible. Herein we review up to date knowledge and emerging evidence on: the mechanisms contributing to HIV persistence, as well as potential strategies to overcome these barriers; promising immunological approaches to achieve viral control and elimination of reservoir-harboring cells, including harnessing adaptive immune responses to HIV and engineered therapies, as well as enhancers of their functions and of complementary innate immune functioning; and combination strategies that are most likely to succeed. Ultimately, a cure must be safe, effective, durable, and, eventually, scalable in order to be widely acceptable and available.

Targeting tau only extracellularly is likely to be less efficacious than targeting it both intra- and extracellularly.

Aggregation of the tau protein is thought to be responsible for the neurodegeneration and subsequent functional impairments in diseases that are collectively named tauopathies. Alzheimer's disease is the most common tauopathy, but the group consists of over 20 different diseases, many of which have tau pathology as their primary feature. The development of tau therapies has mainly focused on preventing the formation of and/or clearing these aggregates. Of these, immunotherapies that aim to either elicit endogenous tau antibodies or deliver exogenous ones are the most common approach in clinical trials. While their mechanism of action can involve several pathways, both extra- and intracellular, pharmaceutical companies have primarily focused on antibody-mediated clearance of extracellular tau. As we have pointed out over the years, this is rather surprising because it is well known that most of pathological tau protein is found intracellularly. It has been repeatedly shown by several groups over the past decades that antibodies can enter neurons and that their cellular uptake can be enhanced by various means, particularly by altering their charge. Here, we will briefly describe the potential extra- and intracellular mechanisms involved in antibody-mediated clearance of tau pathology, discuss these in the context of recent failures of some of the tau antibody trials, and finally provide a brief overview of how the intracellular efficacy of tau antibodies can potentially be further improved by certain modifications that aim to enhance tau clearance via specific intracellular degradation pathways.

Immune-related adverse events of antibody-based biological medicines in cancer therapy.

Recombinant antibodies (Abs) are an integral modality for the treatment of multiple tumour malignancies. Since the Food and Drug Administration (FDA) approval of rituximab as the first monoclonal antibody (mAb) for cancer treatment, several mAbs and antibody (Ab)-based therapies have been approved for the treatment of solid tumour malignancies and other cancers. These Abs function by either blocking oncogenic pathways or angiogenesis, modulating immune response, or by delivering a conjugated drug. The use of Ab-based therapy in cancer patients who could benefit from the treatment, however, is still limited by associated toxicity profiles which may stem from biological features and processes related to target binding, alongside biochemical and/or biophysical characteristics of the therapeutic Ab. A significant immune-related adverse event (irAE) associated with Ab-based therapies is cytokine release syndrome (CRS), characterized by the development of fever, rash and even marked, life-threatening hypotension, and acute inflammation with secondary to systemic uncontrolled increase in a range of pro-inflammatory cytokines. Here, we review irAEs associated with specific classes of approved, Ab-based novel cancer immunotherapeutics, namely immune checkpoint (IC)-targeting Abs, bispecific Abs (BsAbs) and Ab-drug-conjugates (ADCs), highlighting the significance of harmonization in preclinical assay development for safety assessment of Ab-based biotherapeutics as an approach to support and refine clinical translation.

Ubiquitination and deubiquitination in cancer: from mechanisms to novel therapeutic approaches.

Ubiquitination, a pivotal posttranslational modification of proteins, plays a fundamental role in regulating protein stability. The dysregulation of ubiquitinating and deubiquitinating enzymes is a common feature in various cancers, underscoring the imperative to investigate ubiquitin ligases and deubiquitinases (DUBs) for insights into oncogenic processes and the development of therapeutic interventions. In this review, we discuss the contributions of the ubiquitin-proteasome system (UPS) in all hallmarks of cancer and progress in drug discovery. We delve into the multiple functions of the UPS in oncology, including its regulation of multiple cancer-associated pathways, its role in metabolic reprogramming, its engagement with tumor immune responses, its function in phenotypic plasticity and polymorphic microbiomes, and other essential cellular functions. Furthermore, we provide a comprehensive overview of novel anticancer strategies that leverage the UPS, including the development and application of proteolysis targeting chimeras (PROTACs) and molecular glues.

Biomarkers for diagnosis and therapeutic options in hepatocellular carcinoma.

Liver cancer is a global health challenge, causing a significant social-economic burden. Hepatocellular carcinoma (HCC) is the predominant type of primary liver cancer, which is highly heterogeneous in terms of molecular and cellular signatures. Early-stage or small tumors are typically treated with surgery or ablation. Currently, chemotherapies and immunotherapies are the best treatments for unresectable tumors or advanced HCC. However, drug response and acquired resistance are not predictable with the existing systematic guidelines regarding mutation patterns and molecular biomarkers, resulting in sub-optimal treatment outcomes for many patients with atypical molecular profiles. With advanced technological platforms, valuable information such as tumor genetic alterations, epigenetic data, and tumor microenvironments can be obtained from liquid biopsy. The inter- and intra-tumoral heterogeneity of HCC are illustrated, and these collective data provide solid evidence in the decision-making process of treatment regimens. This article reviews the current understanding of HCC detection methods and aims to update the development of HCC surveillance using liquid biopsy. Recent critical findings on the molecular basis, epigenetic profiles, circulating tumor cells, circulating DNAs, and omics studies are elaborated for HCC diagnosis. Besides, biomarkers related to the choice of therapeutic options are discussed. Some notable recent clinical trials working on targeted therapies are also highlighted. Insights are provided to translate the knowledge into potential biomarkers for detection and diagnosis, prognosis, treatment response, and drug resistance indicators in clinical practice.

The American Cancer Society National Lung Cancer Roundtable strategic plan: Advancing comprehensive biomarker testing in non-small cell lung cancer.

Comprehensive biomarker testing is a crucial requirement for the optimal treatment of advanced-stage non-small cell lung cancer (NSCLC), with emerging relevance in the adjuvant treatment setting. To advance its goal of ensuring optimal therapy for persons diagnosed with lung cancer, the American Cancer Society National Lung Cancer Roundtable (ACS NLCRT) held The Summit on Optimizing Lung Cancer Biomarkers in Practice in September 2020 to align its partners toward the goal of ensuring comprehensive biomarker testing for all eligible patients with NSCLC. The ACS NLCRT's Strategic Plan for Advancing Comprehensive Biomarker Testing in NSCLC, a product of the summit, comprises actions to promote comprehensive biomarker testing for all eligible patients. The approach is multifaceted, including policy-level advocacy and the development and dissemination of targeted educational materials, clinical decision tools, and guides to patients, physicians, and payers aimed at ameliorating barriers to testing experienced by each of these groups. PLAIN LANGUAGE SUMMARY: The ACS NLCRT works to improve care for patients with lung cancer. The ACS NLCRT supports comprehensive biomarker testing as essential to determine treatment options for all eligible patients with non-small cell lung cancer. Many factors lead to some patients not receiving optimal biomarker testing. The ACS NLCRT held a collaborative summit and developed a strategic plan to achieve and promote comprehensive biomarker testing for all patients. These plans include developing educational materials and physician tools and advocating for national policies in support of biomarker testing.

Oral administration of CXCL12-expressing Limosilactobacillus reuteri improves colitis by local immunomodulatory actions in preclinical models.

Treatments of colitis, inflammation of the intestine, rely on induction of immune suppression associated with systemic adverse events, including recurrent infections. This treatment strategy is specifically problematic in the increasing population of patients with cancer with immune checkpoint inhibitor (ICI)-induced colitis, as immune suppression also interferes with the ICI-treatment response. Thus, there is a need for local-acting treatments that reduce inflammation and enhance intestinal healing. Here, we investigated the effect and safety of bacterial delivery of short-lived immunomodulating chemokines to the inflamed intestine in mice with colitis. Colitis was induced by dextran sulfate sodium (DSS) alone or in combination with ICI (anti-PD1 and anti-CTLA-4), and Limosilactobacillus reuteri R2LC (L. reuteri R2LC) genetically modified to express the chemokine CXCL12-1α (R2LC_CXCL12, emilimogene sigulactibac) was given perorally. In addition, the pharmacology and safety of the formulated drug candidate, ILP100-Oral, were evaluated in rabbits. Peroral CXCL12-producing L. reuteri R2LC significantly improved colitis symptoms already after 2 days in mice with overt DSS and ICI-induced colitis, which in benchmarking experiments was demonstrated to be superior to treatments with anti-TNF-α, anti-α4ß7, and corticosteroids. The mechanism of action involved chemokine delivery to Peyer's patches (PPs), confirmed by local CXCR4 signaling, and increased numbers of colonic, regulatory immune cells expressing IL-10 and TGF-ß1. No systemic exposure or engraftment could be detected in mice, and product feasibility, pharmacology, and safety were confirmed in rabbits. In conclusion, peroral CXCL12-producing L. reuteri R2LC efficiently ameliorates colitis, enhances mucosal healing, and has a favorable safety profile.NEW & NOTEWORTHY Colitis symptoms are efficiently reduced by peroral administration of probiotic bacteria genetically modified to deliver CXCL12 locally to the inflamed intestine in several mouse models.

Immunomodulation under the lens of real-time in vivo imaging.

Modulation of cells and molecules of the immune system not only represents a major opportunity to treat a variety of diseases including infections, cancer, autoimmune, and inflammatory disorders but could also help understand the intricacies of immune responses. A detailed mechanistic understanding of how a specific immune intervention may provide clinical benefit is essential for the rational design of efficient immunomodulators. Visualizing the impact of immunomodulation in real-time and in vivo has emerged as an important approach to achieve this goal. In this review, we aim to illustrate how multiphoton intravital imaging has helped clarify the mode of action of immunomodulatory strategies such as antibodies or cell therapies. We also discuss how optogenetics combined with imaging will further help manipulate and precisely understand immunomodulatory pathways. Combined with other single-cell technologies, in vivo dynamic imaging has therefore a major potential for guiding preclinical development of immunomodulatory drugs.

Cytokine-induced killer (CIK) cells, successes and challenges: report on the first international conference dedicated to the clinical translation of this unique adoptive cell immunotherapy.

On August 30, 2023, experts from Germany and abroad met to discuss the successes and challenges of cytokine-induced killer cell (CIK) therapy, that recently celebrated its 30th anniversary providing treatment for cancer. This first virtual conference was hosted by CIO Bonn, a certified Comprehensive Cancer Center (CCC) funded by German Cancer Aid (DKH). In addition to keynote speakers involved in CIK cell clinical trials or optimized preclinical models to improve this adoptive cell immunotherapy, more than 100 attendees from around the world also participated in this event. Initiatives to establish the International Society of CIK Cells (ISCC) and a stronger CIK cell network guiding preclinical research and future clinical trials were also announced.

Expanding the reach of commercial cell therapies requires changes at medical centers.

The clinical application of cell therapies is becoming increasingly important for the treatment of cancer, congenital immune deficiencies, and hemoglobinopathies. These therapies have been primarily manufactured and used at academic medical centers. However, cell therapies are now increasingly being produced in centralized manufacturing facilities and shipped to medical centers for administration. Typically, these cell therapies are produced from a patient's own cells, which are the critical starting material. For these therapies to achieve their full potential, more medical centers must develop the infrastructure to collect, label, cryopreserve, test, and ship these cells to the centralized laboratories where these cell therapies are manufactured. Medical centers must also develop systems to receive, store, and infuse the finished cell therapy products. Since most cell therapies are cryopreserved for shipment and storage, medical centers using these therapies will require access to liquid nitrogen product storage tanks and develop procedures to thaw cell therapies. These services could be provided by the hospital pharmacy or transfusion service, but the latter is likely most appropriate. Another barrier to implementing these services is the variability among providers of these cell therapies in the processes related to handling cell therapies. The provision of these services by medical centers would be facilitated by establishing a national coordinating center and a network of apheresis centers to collect and cryopreserve the cells needed to begin the manufacturing process and cell therapy laboratories to store and issue the cells. In addition to organizing cell collections, the coordinating center could establish uniform practices for collecting, labeling, shipping, receiving, thawing, and infusing the cell therapy.

The implication of microbiome in lungs cancer: mechanisms and strategies of cancer growth, diagnosis and therapy.

Available evidence illustrates that microbiome is a promising target for the study of growth, diagnosis and therapy of various types of cancer. Lung cancer is a leading cause of cancer death worldwide. The relationship of microbiota and their products with diverse pathologic conditions has been getting large attention. The novel research suggests that the microbiome plays an important role in the growth and progression of lung cancer. The lung microbiome plays a crucial role in maintaining mucosal immunity and synchronizing the stability between tolerance and inflammation. Alteration in microbiome is identified as a critical player in the progression of lung cancer and negatively impacts the patient. Studies suggest that healthy microbiome is essential for effective therapy. Various clinical trials and research are focusing on enhancing the treatment efficacy by altering the microbiome. The regulation of microbiota will provide innovative and promising treatment strategies for the maintenance of host homeostasis and the prevention of lung cancer in lung cancer patients. In the current review article, we presented the latest progress about the involvement of microbiome in the growth and diagnosis of lung cancer. Furthermore, we also assessed the therapeutic status of the microbiome for the management and treatment of lung cancer.