Tumor Immunotherapy Research Articles

Nanomedicine Remodels Tumor Microenvironment for Solid Tumor Immunotherapy.

Although immunotherapy is relatively effective in treating hematological malignancies, their efficacy against solid tumors is still suboptimal or even noneffective presently. Compared to hematological cancers, solid tumors exhibit strikingly different immunosuppressive microenvironment, severely deteriorating the efficacy of immunotherapy: (1) chemical features such as hypoxia and mild acidity suppress the activity of immune cells, (2) the pro-tumorigenic domestication of immune cells in the microenvironment within the solid tumors further undermines the effectiveness of immunotherapy, and (3) the dense physical barrier of solid tumor tissues prevents the effective intratumoral infiltration and contact killing of active immune cells. Therefore, we believe that reversing the immunosuppressive microenvironment are of critical priority for the immunotherapy against solid tumors. Due to their unique morphologies, structures, and compositions, nanomedicines have become powerful tools for achieving this goal. In this Perspective, we will first briefly introduce the immunosuppressive microenvironment of solid tumors and then summarize the most recent progresses in nanomedicine-based immunotherapy for solid tumors by remodeling tumor immune-microenvironment in a comprehensive manner. It is highly expected that this Perspective will aid in advancing immunotherapy against solid tumors, and we are highly optimistic on the future development in this burgeoning field.

Conserved methylation signatures associate with the tumor immune microenvironment and immunotherapy response

BackgroundAberrant DNA methylation is a major characteristic of cancer genomes. It remains unclear which biological processes determine epigenetic reprogramming and how these processes influence the variants in the cancer methylome, which can further impact cancer phenotypes.MethodsWe performed pairwise permutations of 381,900 loci in 569 paired DNA methylation profiles of cancer tissue and matched normal tissue from The Cancer Genome Atlas (TCGA) and defined conserved differentially methylated positions (DMPs) based on the resulting null distribution. Then, we derived independent methylation signatures from 2,465 cancer-only methylation profiles from the TCGA and 241 cell line-based methylation profiles from the Genomics of Drug Sensitivity in Cancer (GDSC) cohort using nonnegative matrix factorization (NMF). We correlated DNA methylation signatures with various clinical and biological features, including age, survival, cancer stage, tumor immune microenvironment factors, and immunotherapy response. We inferred the determinant genes of these methylation signatures by integrating genomic and transcriptomic data and evaluated the impact of these signatures on cancer phenotypes in independent bulk and single-cell RNA/methylome cohorts.ResultsWe identified 7,364 differentially methylated positions (2,969 Hyper-DMPs and 4,395 Hypo-DMPs) in nine cancer types from the TCGA. We subsequently retrieved three highly conserved, independent methylation signatures (Hyper-MS1, Hypo-MS1, and Hypo-MS4) from cancer tissues and cell lines based on these Hyper and Hypo-DMPs. Our data suggested that Hypo-MS4 activity predicts poor survival and is associated with immunotherapy response and distant tumor metastasis, and Hypo-MS4 activity is related to TP53 mutation and FOXA1 binding specificity. In addition, we demonstrated a correlation between the activities of Hypo-MS4 in cancer cells and the fractions of regulatory CD4 + T cells with the expression levels of immunological genes in the tumor immune microenvironment.ConclusionsOur findings demonstrated that the methylation signatures of distinct biological processes are associated with immune activity in the cancer microenvironment and predict immunotherapy response.

A blood–brain barrier- and blood–brain tumor barrier-penetrating siRNA delivery system targeting gliomas for brain tumor immunotherapy

Glioma is recognized as the most infiltrative and lethal form of central nervous system tumors and is known for its limited response to standard therapeutic interventions, high recurrence rate, and unfavorable prognosis. Recent progress in gene and immunotherapy presents a renewed sense of optimism in the treatment of glioblastoma. However, the barriers to overcome include the blood–brain barrier (BBB) and the blood–brain tumor barrier (BBTB), as well as the suppressive immune microenvironment. Overcoming these barriers remains a significant challenge. Here, we developed a lipid nanoparticle platform incorporating a dual-functional peptide (cholesterol-DP7-ACP-T7-modified DOTAP or DAT-LNP) capable of targeting glioma across the BBB and BBTB for brain tumor immunotherapy. This system was designed to achieve two key functions. First, the system could effectively penetrate the BBB during accumulation within brain tissue following intravenous administration. Second, this system enhances the maturation of dendritic cells, the polarization of M1 macrophages, and the activation of cytotoxic CD8+ T cells. This multifaceted approach effectively mitigates the immunosuppressive tumor microenvironment of glioma and promotes robust antitumor immune responses. Overall, the intravenous administration of the delivery system designed in this study demonstrates significant therapeutic potential for glioma and holds promising applications in the field of cancer immunotherapy.

Efficacy and regulatory strategies of gut microbiota in immunotherapy: a narrative review.

With advances in gut microbiome research, it has been recognized that the gut microbiome has an important and far-reaching impact on many human diseases, including cancer. Therefore, more and more researchers are focusing on the treatment of gut flora in tumors. In this article, we present a review of the mechanisms of gut microbes in tumor immunotherapy and related studies to provide reference for further research and insights into the clinical application of gut microbes. Between April 25, 2023, and November 25, 2023, we searched for articles published only in English between 1984 and 2023 using the databases PubMed, American Medical Association and Elsevier ScienceDirect using the keywords "gut microbiology" and "tumor" or "immunotherapy". The gastrointestinal tract contains the largest number of microorganisms in the human body. Microorganisms are involved in regulating many physiological activities of the body. Studies have shown that gut microbes and their derivatives are involved in the occurrence and development of a variety of inflammations and tumors, and changes in their abundance and proportion affect the degree of cancer progression and sensitivity to immunotherapy. Gut microbiota-based drug research is ongoing, and some anti-tumor studies have entered the clinical trial stage. The abundance and proportion of intestinal microorganisms influence the susceptibility of tumors to tumor immunotherapy. This article reviewed the effects and mechanisms of gut microbes on tumor immunotherapy to further explore the medical value of gut microbes in tumor immunotherapy.

Nanoparticles integrated withmild photothermal therapy and oxaliplatin for tumor chemotherapy and immunotherapy.

Aims: Preparation and evaluation of nanoparticles for tumor chemotherapy and immunotherapy mild photothermal therapy and oxaliplatin. Methods: The double emulsion method was used for nanoparticle preparations. Polydopamine was deposited on the surface, which was further modified with folic acid. Cytotoxicity assays were carried out by cell counting kit-8. In vivo antitumor assays were carried out on 4T1 tumor-bearing mice. Results: The nanoparticles exhibited a 190nm-diameter pomegranate-like sphere, which could increase temperature to 43-46°C. In vivo distribution showed enhanced accumulation. The nanoparticles generated stronger immunogenic cell death effects. By stimulating the maturation of dendritic cells, mild photothermal therapy combined with oxaliplatin significantly increased the antitumor effect by a direct killing effect and activation of immunotherapy. Conclusion: This study provided a promising strategy of combination therapy for tumors.

Cold to Hot: Tumor Immunotherapy by Promoting Vascular Normalization Based on PDGFB Nanocomposites (Small 16/2024)

Cold to Hot: Tumor Immunotherapy by Promoting Vascular Normalization Based on PDGFB Nanocomposites (Small 16/2024)

Identification of genetic modifiers enhancing B7-H3-targeting CAR T cell therapy against glioblastoma through large-scale CRISPRi screening

BackgroundGlioblastoma multiforme (GBM) is a highly aggressive brain tumor with a poor prognosis. Current treatment options are limited and often ineffective. CAR T cell therapy has shown success in treating hematologic malignancies, and there is growing interest in its potential application in solid tumors, including GBM. However, current CAR T therapy lacks clinical efficacy against GBM due to tumor-related resistance mechanisms and CAR T cell deficiencies. Therefore, there is a need to improve CAR T cell therapy efficacy in GBM.MethodsWe conducted large-scale CRISPR interference (CRISPRi) screens in GBM cell line U87 MG cells co-cultured with B7-H3 targeting CAR T cells to identify genetic modifiers that can enhance CAR T cell-mediated tumor killing. Flow cytometry-based tumor killing assay and CAR T cell activation assay were performed to validate screening hits. Bioinformatic analyses on bulk and single-cell RNA sequencing data and the TCGA database were employed to elucidate the mechanism underlying enhanced CAR T efficacy upon knocking down the selected screening hits in U87 MG cells.ResultsWe established B7-H3 as a targetable antigen for CAR T therapy in GBM. Through large-scale CRISPRi screening, we discovered genetic modifiers in GBM cells, including ARPC4, PI4KA, ATP6V1A, UBA1, and NDUFV1, that regulated the efficacy of CAR T cell-mediated tumor killing. Furthermore, we discovered that TNFSF15 was upregulated in both ARPC4 and NDUFV1 knockdown GBM cells and revealed an immunostimulatory role of TNFSF15 in modulating tumor-CAR T interaction to enhance CAR T cell efficacy.ConclusionsOur study highlights the power of CRISPR-based genetic screening in investigating tumor-CAR T interaction and identifies potential druggable targets in tumor cells that confer resistance to CAR T cell killing. Furthermore, we devised targeted strategies that synergize with CAR T therapy against GBM. These findings shed light on the development of novel combinatorial strategies for effective immunotherapy of GBM and other solid tumors.

Inside Back Cover: Near‐infrared laser‐activated aggregation‐induced emission nanoparticles boost tumor carbonyl stress and immunotherapy of breast cancer

Inside Back Cover: Near‐infrared laser‐activated aggregation‐induced emission nanoparticles boost tumor carbonyl stress and immunotherapy of breast cancer

Pan-cancer analyses of immunogenic cell death-derived gene signatures: Potential biomarkers for prognosis and immunotherapy.

Immunogenic cell death (ICD) is a type of regulated cell death that is capable of initiating an adaptive immune response. Induction of ICD may be a potential treatment strategy, as it has been demonstrated to activate the tumor-specific immune response. The biomarkers of ICD and their relationships with the tumor microenvironment, clinical features, and immunotherapy response are not fully understood in a clinical context. Therefore, we conducted pan-cancer analyses of ICD gene signatures across 33 cancer types from The Cancer Genome Atlas database. We identified key genes that had strong relationships with survival and the tumor microenvironment, contributing to a better understanding of the role of ICD genes in cancer therapy. In addition, we predicted therapeutic agents that target ICD genes and explored the potential mechanisms by which gemcitabine induce ICD. Moreover, we developed an ICD score based on the ICD genes and found it to be associated with patient prognosis, clinical features, tumor microenvironment, radiotherapy access, and immunotherapy response. A high ICD score was linked to the immune-hot phenotype, while a low ICD score was linked to the immune-cold phenotype. We uncovered the potential of ICD gene signatures as comprehensive biomarkers for ICD in pan-cancer. Our research provides novel insights into immuno-phenotypic assessment and cancer therapeutic strategies, which could help to broaden the application of immunotherapy to benefit more patients.

A multi-mode Rhein-based nano-platform synergizing ferrotherapy/chemotherapy-induced immunotherapy for enhanced tumor therapy

Ferroptosis has emerged as a promising strategy for treating triple-negative breast cancer (TNBC) due to bypassing apoptosis and triggering immunogenic cell death (ICD) of tumor cells. However, the antitumor efficacy has been limited by the insufficient intracellular ferrous iron concentration required for ferroptosis and inadequate antitumor immune response. To address these limitations, we designed a multi-mode nano-platform (MP-FA@R-F NPs), which exhibited a synergistic effect of ferroptosis, apoptosis and induced immune response for enhanced antitumor therapy. MP-FA@R-F NPs target folate receptors, which are over-expressed on the tumor cell's surface to promote intracellular uptake. The cargoes, including Rhein and Fe3O4, would be released in intracellular acid, accelerating by NIR laser irradiation. The released Rhein induced apoptosis of tumor cells mediated by the caspase 3 signal pathway, while the released Fe3O4 triggered ferroptosis through the Fenton reaction and endowed the nanoplatform with magnetic resonance imaging (MRI) capabilities. In addition, ferroptosis-dying tumor cells could release damage-associated molecular patterns (DAMPs) to promote T cell activation and infiltration for immune response and induce immunogenic cell death (ICD) for tumor immunotherapy. Together, MP-FA@R-F NPs represent a potential synergistic ferro-/chemo-/immuno-therapy strategy with MRI guidance for enhanced antitumor therapy. Statement of significanceThe massive strategies of cancer therapy based on ferroptosis have been emerging in recent years, which provided new insights into designing materials for cancer therapy. However, the antitumor efficacy of ferroptosis is still unsatisfactory, mainly due to insufficient intracellular pro-ferroptotic stimuli. In the current study, we designed a multi-mode nano-platform (MP-FA@R-F NPs), which represented a potential synergistic ferro-/chemo-/immuno-therapy strategy with MRI guidance for enhanced antitumor therapy.

T Cell Receptor-Directed Bispecific T Cell Engager Targeting MHC-Linked NY-ESO-1 for Tumor Immunotherapy.

Antibody-based bispecific T cell engagers (TCEs) that redirect T cells to kill tumor cells have shown a promising therapeutic effect on hematologic malignancies. However, tumor-specific targeting is still a challenge for TCEs, impeding the development of TCEs for solid tumor therapy. The major histocompatibility complex (MHC) presents almost all intracellular peptides (including tumor-specific peptides) on the cell surface to be scanned by the TCR on T cells. With the premise of choosing optimal peptides, the final complex peptide-MHC could be the tumor-specific target for TCEs. Here, a novel TCR-directed format of a TCE targeting peptide-MHC was designed named IgG-T-TCE, which was modified from the IgG backbone and prepared in a mammalian cell expression system. The recombinant IgG-T-TCE-NY targeting NY-ESO-1157-165/HLA-A*02:01 could be generated in HEK293 cells with a glycosylated TCR and showed potency in T cell activation and redirecting T cells to specifically kill target tumor cells. We also found that the in vitro activity of IgG-T-TCE-NY could be leveraged by various anti-CD3 antibodies and Fc silencing. The IgG-T-TCE-NY efficiently inhibited tumor growth in a tumor-PBMC co-engrafted mouse model without any obvious toxicities.

Spatiotemporally-controlled supramolecular hybrid nanoassembly enabling ferroptosis-augmented photodynamic immunotherapy of cancer

Photodynamic therapy (PDT) not only directly eradicates tumor cells but also boosts immunogenicity, promoting antigen presentation and immune cell infiltration. However, the robust antioxidant defense mechanisms within tumor cells significantly weaken the efficacy of photodynamic immunotherapy. Herein, a supramolecular hybrid nanoassembly is constructed by exploring the synergistic effects of the photodynamic photosensitizer (pyropheophorbide a, PPa) and the ferroptosis inducer (erastin). The erastin-mediated inhibition of system Xc− significantly downregulates glutathione (GSH) expression, amplifying intracellular oxidative stress, leading to pronounced cell apoptosis, and promoting the release of damage-associated molecular patterns (DAMPs). Additionally, the precise cooperation of PPa and erastin enhances ferroptosis efficiency, exacerbating the accumulation of lipid peroxides (LPOs). Ultimately, LPOs serve as a “find me” signal, while DMAPs act as an “eat me” signal, collectively promoting dendritic cell maturation, enhancing infiltration of the cytotoxic T lymphocytes, and eliciting a robust immune response. This study opens new horizons for enhancing tumor immunotherapy through simultaneous ferroptosis-PDT.

Role of TBK1 Inhibition in Targeted Therapy of Cancer.

TANK-binding kinase 1 (TBK1) is a serine/threonine protein that plays a crucial role in various biological processes like immunity, autophagy, cell survival, and proliferation. The level and kinase activity of the TBK1 protein is regulated through post-translational modifications (PTMs). TBK1 mainly mediates the activation of IRF3/7 and NF-κB signaling pathways while also participating in the regulation of cellular activities such as autophagy, mitochondrial metabolism, and cell proliferation. TBK1 regulates immune, metabolic, inflammatory, and tumor occurrence and development within the body through these cellular activities. TBK1 kinase has emerged as a promising therapeutic target for tumor immunity. However, its molecular mechanism of action remains largely unknown. The identification of selective TBK1 small molecule inhibitors can serve as valuable tools for investigating the biological function of TBK1 protein and also as potential drug candidates for tumor immunotherapy. The current research progress indicates that some TBK1 inhibitors (compounds 15,16 and 21) exhibit certain antitumor effects in vitro culture systems. Here, we summarize the mechanism of action of TBK1 in tumors in recent years and the progress of small molecule inhibitors of TBK1.

An antitumor fungal polysaccharide from Fomitopsis officinalis by activating immunity and inhibiting angiogenesis

Macrofungi, a class of unique natural resources, are gaining popularity owing to their potential therapeutic benefits and edibility. From Fomitopsis officinalis, a medicinal macrofungus with anticancer activity, a homogeneous heteropolysaccharide (FOBP50–1) with a molecular weight of 2.21 × 104 g/mol has been extracted and purified. FOBP50–1 was found to be composed of 3-O-methylfucose, fucose, mannose, glucose, and galactose with a ratio of 1: 6.5: 4.4: 8.1: 18.2. The sugar fragments and structure of FOBP50–1 were investigated, which included →6)-α-d-Galp-(1→, →2,6)-α-d-Galp-(1→, →3)-α-l-Fucp-(1→, α-d-Glcp-(1→, →3)-β-d-Manp-(1→, →6)-β-d-Manp-(1→, 3-O-Me-α-l-Fucp-(1→, according to the UV, FT-IR, GC–MS, and NMR data. Besides the structure elucidation, FOBP50–1 showed promising antitumor activity in the zebrafish assays. The following mechanism examination discovered that FOBP50–1 interacted with TLR-4, PD-1, and VEGF to activate immunity and inhibit angiogenesis according to a series of cell, transgenic zebrafish, and surface plasmon resonance (SPR) experiments. The KD values indicating the association of FOBP50–1 with TLR-4, PD-1, and VEGF, were 4.69 × 10−5, 7.98 × 10−6, 3.04 × 10−6 M, respectively, in the SPR experiments. All investigations have demonstrated that the homogenous fungal polysaccharide FOBP50–1 has the potential to be turned into a tumor immunotherapy agent.

Ultra-small Janus nanoparticle-induced activation of ferroptosis for synergistic tumor immunotherapy

Ferroptosis induced by lipid peroxide (LPO) accumulation is an effective cell death pathway for cancer therapy. However, how to effectively induce ferroptosis at tumor sites and improve its therapeutic effectiveness remains challenging. Here, MnFe2O4@NaGdF4@NLG919@HA (MGNH) nanocomplex with tumor-specific targeting and TME response is constructed to overcome immunosuppressive tumor microenvironment (TME) to potentiate the curative effect of ferroptosis by coupling the immune checkpoint indoleamine 2,3-dioxygenase (IDO) inhibitor, NLG919, and hyaluronic acid (HA) to novel ultra-small MnFe2O4@NaGdF4 (MG) nanoparticles with a Janus structure. Firstly, tumor site-precise delivery of MG and NLG919 is achieved with HA targeting. Secondly, MG acts as a magnetic resonance imaging contrast agent, which not only has a good photothermal effect to realize tumor photothermal therapy, but also depletes glutathione and catalyzes the production of reactive oxygen species from endogenous H2O2, which effectively promotes the accumulation of LPO and inhibits the expression of glutathione peroxidase 4, achieving enhanced ferroptosis. Thirdly, NLG919 inhibits the differentiation of Tregs by blocking the tryptophan/kynurenine immune escape pathway, thereby reversing immunosuppressive TME together with the Mn2+-activated cGAS-STING pathway. This work contributes new perspectives for the development of novel ultra-small Janus nanoparticles to reshape immunosuppressive TME and ferroptosis activation. Statement of significanceThe Janus structured MnFe2O4@NaGdF4@NLG919@HA (MGNH) nanocomplex was synthesized, which can realize the precise delivery of T1/T2 contrast agents MnFe2O4@NaGdF4 (MG) and NLG919 at the tumor site under the ultra-small Janus structural characteristics and targeted molecule HA. The production of ROS, consumption of GSH, and photothermal properties of MGNH make it possible for CDT/PTT activated ferroptosis, and synergistically disrupt and reprogram tumor growth and immunosuppressive tumor microenvironment with NLG919 and Mn2+-mediated activation of cGAS-STING pathway, achieving CDT/PTT/immunotherapy activated by ferroptosis. Meanwhile, ultra-small structural properties of MGNH facilitate subsequent metabolic clearance by the body, allowing for the minimization of potential biotoxicity associated with its prolonged retention.

Pan-cancer prognostic model and immune microenvironment analysis of natural killer cell-related genes.

Natural killer (NK) cells play a significant role in antitumor immunity and are closely related to tumor prognosis and recurrence. NK cell-based tumor immunotherapy, including immune checkpoint inhibition and CAR-engineered NK cells, is a promising area of research. However, there is a need for better NK cell-related models and associated biomarkers. The sequences of NK cell-related genes were obtained from the published NK cell CRISPR/Cas9 library data, and the common genes were selected as NK cell-related genes. The RNA sequencing (RNA-seq) and clinical data of 32 solid tumors from The Cancer Genome Atlas (TCGA) were downloaded from the UCSC Xena database, and the RNA-seq data of normal samples were downloaded from the Genotype-Tissue Expression (GTEx) database. The differentially expressed NK cell-related genes (DENKGs) between the tumor and normal samples were analyzed. The DENKGs related to the prognosis of solid tumors were selected via univariate Cox analysis, and 32 kinds of solid tumor prognostic models were constructed using least absolute shrinkage and selection operator (LASSO) and multivariate Cox analysis. Survival, receiver operating characteristic (ROC), and independent prognostic analyses were employed to test the effectiveness of the model, along with a nomogram model and prediction curve. Differences in the immune pathways and microenvironment cells were analyzed between the high- and low-risk groups identified by the model. We constructed a pan-cancer prognostic model with 63 NK cell-related genes and further identified DEPDC1 and ASPM as potentially offering new directions in tumor research by literature screening. In this study, 63 prognostic solid tumor markers were investigated using NK cell-related genes, and for the first time, a pan-cancer prognostic model was constructed to analyze their role in the immune microenvironment, which may contribute new insights into tumor research.

The Immune Microenvironment and Immune Therapy Response Mechanism of Renal Clear Cell Carcinoma

The purpose of this article is to study the immune microenvironment characteristics of renal clear cell tumor and the application effect of immunotherapy in this tumor. In order to achieve this goal, this article adopts systematic experimental methods and analytical means. Firstly, the distribution of tumor infiltrating immune cells and the expression of key immune molecules were described in detail by collecting renal clear cell tumor samples and using flow cytometry, immunohistochemistry and other technical means. Subsequently, in vitro and in vivo experiments of immunotherapy were designed and implemented to evaluate the anti-tumor effects of different immunotherapy strategies. The experimental results show that the immune microenvironment of renal clear cell tumor presents unique characteristics, including the infiltration mode of immune cells and the expression profile of immune molecules. Both in vitro and in vivo immunotherapy experiments show that some immunotherapy strategies can effectively inhibit the growth of renal clear cell tumor and prolong the survival time of animal models. Based on the above findings, it can be concluded that the immune microenvironment of renal clear cell tumor plays a key role in tumor progression and immunotherapy response. A deep understanding of the characteristics and regulation mechanism of immune microenvironment is helpful to develop more effective immunotherapy strategies.

New insights into the role of macrophages in cancer immunotherapy.

Macrophages are the main component of the tumor microenvironment, which are differentiated from monocytes in the blood and play an important role in cancer development. Tumor-associated macrophages (TAMs) can promote tumor growth, invasion, metastasis, and resistance to anti-programmed death receptor 1 therapy by regulating programmed cell death ligand 1 expression and interacting with other immune cells in the tumor microenvironment. However, when activated properly, macrophages can also play an anti-tumor role by enhancing the phagocytosis and cytotoxicity of tumor cells. TAM is associated with poor prognosis and drug resistance in patients treated with immunotherapy, indicating that macrophages are attractive targets for combined therapy in cancer treatment. Combination of targeting TAMs and immunotherapy overcomes the drug resistance and achieved excellent results in some cancers, which may be a promising strategy for cancer treatment in the future. Herein, we review the recent findings on the role of macrophages in tumor development, metastasis, and immunotherapy. We focus mainly on macrophage≥centered therapy, including strategies to deplete and reprogram TAMs, which represent the potential targets for improving tumor immunotherapy efficacy.

Exploring the regulatory mechanism of intestinal flora based on PD-1 receptor/ligand targeted cancer immunotherapy.

Serving as a pivotal immunotherapeutic approach against tumors, anti-PD-1/PD-L1 therapy amplifies the immune cells' capability to eliminate tumors by obstructing the interaction between PD-1 and PD-L1. Research indicates that immune checkpoint inhibitors are effective when a patient's gut harbors unique beneficial bacteria. As such, it has further been revealed that the gut microbiome influences tumor development and the efficacy of cancer treatments, with metabolites produced by the microbiome playing a regulatory role in the antitumor efficacy of Immune checkpoint inhibitors(ICBs). This article discusses the mechanism of anti-PD-1 immunotherapy and the role of intestinal flora in immune regulation. This review focuses on the modulation of intestinal flora in the context of PD-1 immunotherapy, which may offer a new avenue for combination therapy in tumor immunotherapy.

A commentary on 'Worldwide research trends on tumor burden and immunotherapy: A bibliometric analysis'.

A commentary on 'Worldwide research trends on tumor burden and immunotherapy: A bibliometric analysis'.