Bidirectional crosstalk between therapeutic cancer vaccines and the tumor microenvironment: Beyond tumor antigens

BackgroundTumor vaccines have become crucial in cancer immunotherapy, but, only a limited number of phase III clinical trials have demonstrated clinical efficacy. The crux of this issue is the inability of tumor vaccines to effectively harmonize the tumor microenvironment with its intricate interplay. One factor that can hinder the effectiveness of vaccines is the natural immunosuppressive element present in the tumor microenvironment. This element can lead to low rates of T-cell response specific to antigens and the development of acquired resistance. Conversely, anticancer vaccines alter the tumor microenvironment in conflicting manners, inducing both immune activation and immunological evasion. Hence, comprehending the correlation between tumor vaccines and the tumor microenvironment would establish a foundation for forthcoming tumor treatment.ObjectiveOur review explores the realm of research pertaining to tumor vaccinations and the tumor microenvironment. Our objective is to investigate the correlation between tumor vaccines and the tumor microenvironment within this domain. We then focus our review on the dominant international paradigms in this research field and visually illustrates the historical progression and emergent patterns observed in the past.MethodsFrom January 1, 1999 to February 7, 2023, 1420 articles on the interplay between tumor vaccines and the tumor microenvironment were published, according to The Clarivate Web of Science (WOS) database used in our review. A bibliometric review was designed for this collection and consisted of an evaluation. The evaluation encompassed various discernible attributes, including the year of publication, the journals in which the articles were published, the authors involved, the affiliated institutions, the geographical locations of the institutions, the references cited, and the keywords employed.ResultsBetween the years 1999 and 2022, publications saw a significant increase, from 3 to 265 annually. With 72 papers published, Frontiers in Immunology had the most manuscripts published. The Cancer Research publication garnered the highest number of citations, amounting to 2874 citations. The United States exerts significant dominance in the subject, with the National Cancer Institute being recognized as a prominent institution in terms of both productivity and influence. Furthermore, Elizabeth M. Jaffee was recognized as the field’s most prolific and influential author with 24 publications and 1,756 citations. The co-occurrence cluster analysis was conducted on the top 197 keywords, resulting in the identification of five distinct clusters. The most recent high-frequency keywords, namely immune therapy, dendritic cell, tumor microenvironment, cancer, and vaccine, signify the emerging frontiers in the interaction between tumor vaccines and the tumor microenvironment.ConclusionOur review uncovers insights into contemporary trends, global patterns of collaboration, fundamental knowledge, research areas of high interest, and emerging frontiers in the field of TME-targeted vaccines.

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Global trends in tumor microenvironment-related research on tumor vaccine: a review and bibliometric analysis

Liu,

Li,

Chen

et al. 2024

“…By detecting the expression levels of key biomarkers and taking into account the clinical characteristics of patients, it is important to predict the prognosis of patients (91). Furthermore, emerging nanoformulations and tumor antigen vaccines have demonstrated high specificity and efficiency (92,93). Guan L et al synthesized mesoporous organosilicon nanoparticles exhibiting robust antitumor abilities and biosafety (94).…”

Section: Discussionmentioning

confidence: 99%

Single-cell disulfidptosis regulator patterns guide intercellular communication of tumor microenvironment that contribute to kidney renal clear cell carcinoma progression and immunotherapy

Xu,

Li,

Qian

et al. 2024

BackgroundDisulfidptosis, an emerging type of programmed cell death, plays a pivotal role in various cancer types, notably impacting the progression of kidney renal clear cell carcinoma (KIRC) through the tumor microenvironment (TME). However, the specific involvement of disulfidptosis within the TME remains elusive.MethodsAnalyzing 41,784 single cells obtained from seven samples of KIRC through single-cell RNA sequencing (scRNA-seq), this study employed nonnegative matrix factorization (NMF) to assess 24 disulfidptosis regulators. Pseudotime analysis, intercellular communication mapping, determination of transcription factor activities (TFs), and metabolic profiling of the TME subgroup in KIRC were conducted using Monocle, CellChat, SCENIC, and scMetabolism. Additionally, public cohorts were utilized to predict prognosis and immune responses within the TME subgroup of KIRC.ResultsThrough NMF clustering and differential expression marker genes, fibroblasts, macrophages, monocytes, T cells, and B cells were categorized into four to six distinct subgroups. Furthermore, this investigation revealed the correlation between disulfidptosis regulatory factors and the biological traits, as well as the pseudotime trajectories of TME subgroups. Notably, disulfidptosis-mediated TME subgroups (DSTN+CD4T-C1 and FLNA+CD4T-C2) demonstrated significant prognostic value and immune responses in patients with KIRC. Multiple immunohistochemistry (mIHC) assays identified marker expression within both cell clusters. Moreover, CellChat analysis unveiled diverse and extensive interactions between disulfidptosis-mediated TME subgroups and tumor epithelial cells, highlighting the TNFSF12-TNFRSF12A ligand-receptor pair as mediators between DSTN+CD4T-C1, FLNA+CD4T-C2, and epithelial cells.ConclusionOur study sheds light on the role of disulfidptosis-mediated intercellular communication in regulating the biological characteristics of the TME. These findings offer valuable insights for patients with KIRC, potentially guiding personalized immunotherapy approaches.

“…Characteristics of TME include hypoxia, immunosuppression, chronic inflammation, acidosis, high interstitial fluid pressure, increased ECM stiffness, and depletion of essential nutrients. Immunotherapy mainly targets hypoxia and immunosuppression, which are presently active research topics (41). Precision medicine aims to develop targeted and immunotherapies to enhance the survival rate.…”

Section: Discussionmentioning

confidence: 99%

Multi-omics analysis reveals the involvement of origin recognition complex subunit 6 in tumor immune regulation and malignant progression

Zhu,

Chen,

Zeng

et al. 2023

BackgroundOrigin recognition complex 6 (ORC6) is one of the six highly conserved subunit proteins required for DNA replication and is essential for maintaining genome stability during cell division. Recent research shows that ORC6 regulates the advancement of multiple cancers; however, it remains unclear what regulatory impact it has on the tumor immune microenvironment.MethodsUnpaired Wilcoxon rank sum and signed rank tests were used to analyze the differences in the expression of ORC6 in normal tissues and corresponding tumor tissues. Multiple online databases have evaluated the genetic alterations, protein expression and localization, and clinical relevance of ORC6. To evaluate the potential prognostic impact and diagnostic significance of ORC6 expression, we carried out log-rank, univariate Cox regression, and receiver operating characteristic curve analysis. The ICGC-LIRI-JP cohort, CGGA-301 cohort, CGGA-325 cohort, CGGA-693 cohort, and GSE13041 cohort were used for external validation of the study findings. The associations between ORC6 expression and immune cell infiltration, immune checkpoint expression, and immunotherapy cohorts was further analyzed. To explore the functional and signaling pathways related to ORC6 expression, gene set enrichment analysis was performed. To clarify the expression and function of ORC6 in hepatocellular carcinoma (LIHC) and glioma, we conducted in vitro experiments.ResultsExpression of ORC6 is upregulated in the majority of cancer types and is associated with poor patient prognosis, notably in cases of LIHC and gliomas. In addition, ORC6 may be involved in multiple signaling pathways related to cancer progression and immune regulation. High expression of ORC6 correlates with an immunosuppressive state in the tumor microenvironment. The results of further immunotherapy cohort analysis suggested that patients in the ORC6 high-expression group benefited from immunotherapy. Inhibiting ORC6 expression suppressed the proliferative and migratory abilities of LIHC and glioma cells.ConclusionHigh expression of ORC6 may be used as a biomarker to predict the poor prognosis of most tumor patients. The high expression of ORC6 may be involved in the regulation of the tumor immunosuppressive environment, and it is expected to become a molecular target for inhibiting tumor progression.