Trends and hotspots in research related to tumor immune escape: bibliometric analysis and future perspectives

Bibliometric analysis offers a systematic framework for identifying developmental trends and research hotspots within a discipline over a defined period. The selection of an appropriate database is critical to ensuring data reliability and analytical rigor. Among available options, the Web of Science (WoS) stands out for its multidisciplinary coverage of high-impact scientific journals and robust citation indexing. Compared to Scopus and MEDLINE/PubMed, WoS provides more comprehensive information that is particularly well-suited for bibliometric analysis (17). In this study, we selected the Web of Science Core Collection as our primary data source, as it is widely recognized for its depth, accuracy, and authority in indexing peer-reviewed literature (19). Its extensive journal coverage ensures that the retrieved publications reflect contemporary research trajectories in immunology and oncology. This choice enables accurate, representative data extraction and supports a thorough exploration of valuable research insights.

A literature search was conducted on February 14, 2025, to retrieve original articles and reviews on tumor immune escape published between 2009 and February 14, 2025. To avoid temporal bias due to real-time database updates, the search was completed in a single day. The search strategy was as follows: ((((TS=(“Immune Escape, Tumor”)) OR TS=(“Tumor Immune Escape”) OR TS=(“Tumor Immune Evasion”) OR TS=(“Evasions, Tumor Immune”) OR TS=(“Evasion, Tumor Immune”) OR TS=(“Immune Evasions, Tumor”) OR TS=(“Tumor Immune Evasions”) OR TS=(“Immune Evasion, Tumor”)))). Only journal articles and reviews published in English were included in this analysis. Other publication types—such as letters, editorials, conference abstracts, meeting reports—and all non-English publications were excluded to ensure consistency and comparability of the bibliometric dataset. The eligible records were exported in plain-text format with the “Full Record and Cited References” option selected to enable comprehensive metadata extraction. The final dataset contained information on publication counts, citations, titles, authors, affiliations, countries, keywords, and journals. In total, 1,839 records met the inclusion criteria. The detailed screening process is presented in Figure 1.

For data processing and analysis, we used Microsoft Excel in combination with three specialized tools: Bibliometrix 4.3.3 (an R-based package), VOSviewer 1.6.20, and CiteSpace 6.4.R1.

VOSviewer, developed by van Eck and Waltman, generates bibliometric network visualizations using node-link diagrams. It visualizes collaboration patterns by clustering nodes chromatically, where node size represents publication volume and edge thickness indicates collaboration strength between entities (e.g., countries or institutions).

CiteSpace, created by Chaomei Chen, is a Java-based software for detecting research frontiers. It employs timeline mapping and citation burst detection, with keyword clustering to reveal thematic domains. Clustering reliability is validated when silhouette values exceed 0.5 and modularity Q-values exceed 0.3, indicating strong internal consistency and significant structural separation.

Bibliometrix, an R-integrated package, enables statistical analysis of scholarly outputs including publication frequencies, citation metrics, and national contributions. Its algorithms support cross-comparison among journals and countries, contributing to a quantitative understanding of academic productivity.

As per the formulated research strategy, 1,839 tumor immune escape - related publications were obtained from the WoSCC database between 2009 and 14 February 2025. Figure 2 presents the annual publication and citation counts for tumor immune escape research from 2009 to 14 February 2025.

The steady publication increase from 2009 to 2018 shows great attention and interest in this field. The steeper growth curve from 2018 onwards indicates significant expansion, likely due to the 2018 Nobel Prize in Physiology or Medicine awarded to Professors James P. Allison and Tasuku Honjo for their work on the CTLA - 4 and PD - 1/PD - L1 pathways. The rising citation trend suggests ongoing research impact and the need for more prospective studies to highlight its global relevance.

A total of 65 countries and 2,184 institutions participated in tumor immune escape research. Table 1 ranks the top ten countries by number of publications and total citations. China (n = 958) was the most productive country, accounting for 52.1 per cent of the total number of publications, followed by the United States (n = 281, 15.3 per cent), and Germany (n = 114, 6.2 per cent). The US and China have nearly identical total citations, 28,052 and 28,142 respectively, far surpassing other nations and highlighting their influence in this field. The UK has the highest average citations per publication at 131. Multiple country publication (Figure 3) refers to the proportion of publications in this field involving contributions from multiple countries and is used to assess international collaboration levels within a research area in a given country. China has the highest number of publications, but the proportion of multiple country publication with other countries is relatively low at 13.2%. However, France (43.2%) and the UK (69.6%) have a high proportion of multiple country publication, indicating their significant contributions to international cooperation.

A minimum threshold of 7 articles was set to filter out 30 countries meeting the criteria, as shown in Figures 4A, B. This reveals a wide - ranging network of international cooperation, with the US, China, and various European countries serving as key hubs. The United States led international collaboration with the highest total link strength at 303, underscoring its central role in the global tumor immune-escape network. China followed at 204, and Germany at 117, together highlighting these nations’ pivotal contributions to cross-border research and knowledge exchange in the field. Notably, the closest collaboration exists between the US and China. Additionally, publication timelines were analyzed through a VOSviewer - based visual map of organizational collaboration overlays (Figure 4B). It is worth noting that China started publishing later than most other leading countries in this field.

Among the top 15 institutions ranked by publication count (Table 2), Sun Yat-sen University leads with 72 publications, followed by the Chinese Academy of Sciences with 69. This indicates Sun Yat-sen University has the greatest international influence. These institutions are significant not only in publication quantity but also in impact. Notably, the University of Texas System, despite ranking eighth in publication count (45 publications), holds the top spot in betweenness centrality (0.11 centrality), suggesting its research is highly collaborative internationally and highly influential in tumor immune escape.

Figure 5A shows the top 15 institutions with citation outbreaks. Shandong First Medical University & Shandong Academy of Medical Sciences have recently experienced citation bursts, indicating significant potential in tumor immune escape research. In the co - occurrence graph (Figure 5B), node size represents co - occurrence frequency, and links show co - occurrence relationships. Nodes with purple rounded corners have high betweenness centrality (≥0.1), such as the University of Texas System and UTMD Anderson Cancer Center, which play key roles in connecting diverse research communities.

To identify active and influential journals in tumor immune escape, a visual analysis of published journals was done, uncovering 1,839 related publications in 472 academic journals. FRONTIERS IN IMMUNOLOGY had the most publications (126), followed by CANCERS (54) and CANCER RESEARCH (31) (see Table 3). Notably, CANCER RESEARCH has the highest impact factor (12.5) and average citations (107) among the top 10 journals, underscoring its significant impact in tumor immunology.

Figure 6 Application of Bradford’s Law showing core journals for tumor immune escape research.

The double figure overlay reveals a single citation pathway in numerous inter - field links between journals (Figure 7). Interestingly, publications on MOLECULAR, BIOLOGY, GENETICS are mainly cited by publications on MOLECULAR, BIOLOGY, IMMUNOLOGY and MEDICINE, MEDICAL, CLINICAL.

In this study, 12,322 authors were involved in the study. Table 4 lists the top 10 most prominent authors in tumor immune escape research. Xuitao Cao leads the list with 11 articles and 1737 citations, followed by Kebin Liu with 10 articles and 558 citations. Notably, Li Yong has published fewer articles but has the second highest number of citations. His 2018 publication was the first article on tumor immune escape, marking him as a highly promising emerging figure in the field (Table 4).

Figure 8 illustrates the collaborative network of 45 authors who have published five or more articles. These authors are clustered into five distinct collaborative groups. While each group demonstrates strong internal collaboration, there is limited interaction between groups. This pattern indicates a relative lack of intergroup communication and suggests the need to strengthen inter-institutional and international collaboration within the field.

Table 5 resents the top 10 most cited articles on tumor immune escape. The first two articles, each with over 2,800 citations, lead significantly over the remaining entries, underscoring their substantial influence in the field.

The most cited article globally is ‘Signatures of T cell dysfunction and exclusion predict cancer immunotherapy response’ by Jiang P, published in Nature Medicine in 2018 with 3,151 citations. This article introduces TIDE, an alternative biomarker for predicting immune checkpoint blockade (ICB) response, offering novel ideas for immune checkpoint blockade prediction and laying the foundation for immunotherapy prognosis forecasting (20).

The second most cited article globally is Ansell SM’s ‘PD-1 blockade with nivolumab in relapsed or refractory Hodgkin’s lymphoma’, published in the New England Journal of Medicine in 2015. This study presents nivolumab as a new PD-1 blockade antibody and is the first to evaluate its efficacy and safety in relapsed or refractory Hodgkin’s lymphoma, providing a crucial basis for subsequent clinical applications in combating tumor immune escape (21).

Figure 9A highlights 20 core publications that experienced significant citation bursts, underscoring their influence and cutting-edge contributions to the tumor immune escape field during the analyzed timeframe. Early foundational literature, such as the work by Rabinovich et al. (22), experienced a dramatic citation surge between 2009 and 2011. This article became a landmark in tumor immunology by synthesizing previously fragmented immune escape mechanisms into a unified conceptual framework. It identified key immunotherapeutic targets, addressed unmet needs in immunotherapy research, and catalyzed the translation of basic science into clinical practice. Building upon earlier conceptual frameworks, Hanahan D provided a comprehensive synthesis of the hallmarks of cancer, in which immune evasion was recognized as an emerging hallmark and the TME was emphasized as a critical component influencing tumor progression and therapeutic resistance (23). This conceptual integration laid important theoretical groundwork for subsequent research into the mechanisms of tumor immune escape.

Between 2013 and 2017, three citation burst references were identified, all of which were pivotal clinical trials (24–26). This period marked a significant turning point, as immune checkpoint inhibitors (ICIs) transitioned from preclinical exploration to clinical application. Among these, the landmark study by Hodi FS et al. (26) demonstrated that ipilimumab significantly improved overall survival in patients with advanced melanoma (median OS increased from 6.4 to 10.1 months), leading to its FDA approval in 2011 for metastatic melanoma. Ipilimumab thereby became the first immune checkpoint inhibitor approved globally, inaugurating a new era in cancer immunotherapy. Four additional citation burst articles identified between 2015 and 2020 (21, 27–29) focused on PD-1 inhibitors, likely reflecting the momentum generated by the FDA approvals of nivolumab and pembrolizumab in 2014. These approvals marked a major breakthrough in immunotherapy and spurred a surge of clinical and translational research into immune checkpoint blockade strategies. In 2018, Jiang P and colleagues (20) developed TIDE (Tumor Immune Dysfunction and Exclusion), a computational framework designed to model the two major mechanisms of tumor immune escape and predict responses to ICI therapy. Beyond its direct predictive value, TIDE played a pioneering role in bridging AI and tumor immunology, setting the stage for subsequent applications of machine learning in decoding immune evasion. Notably, this study attracted widespread attention between 2021 and 2023 and remains the most cited article in the field to date, underscoring its foundational significance and groundbreaking impact. The article exhibiting the most intense citation burst was “Global Cancer Statistics 2020: GLOBOCAN Estimates of Incidence and Mortality Worldwide for 36 Cancers in 185 Countries” by Sung H et al. (30), published in 2021 in CA: A Cancer Journal for Clinicians (impact factor: 503.1). Utilizing GLOBOCAN 2020 data, this study provided a comprehensive overview of the global cancer burden, highlighting substantial regional differences in cancer incidence and mortality, and exploring the underlying epidemiological factors. The publication has since served as both an authoritative data source and an essential reference for global oncology research and clinical practice.

The use of co - citation cluster analysis offers an objective illustration of the knowledge structure within a research area. For a more detailed description of the co - cited reference groups, a network diagram was generated. The degree of association between articles was categorized into 17 groups, which formed the basis for the clustering classification. The co - citation cluster analysis, as shown in the diagram, clearly reveals the knowledge structure of the research area. To fully describe the co - cited literature groups, a complex network diagram was constructed (as shown in Figure 9B). Research topics were classified into 17 categories based on co - citation relationships, forming a clear cluster structure. In this diagram, (1) metabolic reprogramming, being the largest cluster, indicates that metabolic reprogramming - related research holds a central position in the field and carries extensive academic influence.

Evidence of evolution over time among the study clusters is also apparent. For instance, the gradual evolution of (4) non-small cell lung cancer clusters into the emergence of (0) tumor-derived exosome, (3) tumor-associated macrophages and (1) metabolic reprogramming clusters. In the field of non-small cell lung cancer research, the transition from conventional to immunotherapeutic approaches has catalyzed the rapid evolution of tumor immunotherapy. Additionally, triple negative breast cancer is the most aggressive breast cancer type, having limited treatment choices and a poor prognosis (31). The figure shows that the triple negative breast cancer group gradually evolved into metabolic reprogramming and tumor-associated macrophage groups. This means immunotherapy breakthroughs bring hope to triple negative breast cancer clinical treatment.

The (7) PD-L1 cohort has gradually evolved into the (3) tumor-associated macrophages and (0) tumor-derived exosomes cohorts, reflecting the research process of tumor immune escape, which further promotes the exploration of the tumor microenvironment due to the differentiated efficacy of PD-L1-targeted drugs. It reflects the in-depth exploration of the mechanism of tumor development and the continuous optimization of immunotherapy strategies in the field of tumor immunity.

Beyond the main evolutionary trends, several smaller groups indicate the ongoing development of specific research directions. Notably, (1) metabolic reprogramming cohorts have gradually evolved into (9) prognosis cohorts. This shift shows that as tumor metabolomics advances, researchers are paying more attention to predicting patient prognosis. Metabolic reprogramming is a key strategy for tumor cells to adapt to harsh microenvironments and maintain rapid proliferation and survival (32, 33). This metabolic alteration not only supports tumor growth but also closely correlates with tumor malignancy and poor patient prognosis (34), providing a solid theoretical basis for the evolution of metabolic reprogramming research towards prognosis. In clinical practice, accurately predicting patient prognosis is crucial for developing personalized treatment plans and improving survival rates.

Figures 10A, B highlight key themes in tumor immune escape research, including ‘immunotherapy’, ‘pd-l1’, ‘cancer’, ‘expression’, ‘tumor microenvironment’, ‘dendritic cells’, and ‘t-cells’. These keywords are strongly interconnected, reflecting their central role in the research community. The density visualization reveals intense research activity around these themes, with warmer colors indicating areas of high interest.

Figures 10C, D depict the evolution of research topics in tumor immune evasion. Figure 10C analysis of theme word trends from 2009 to 2025 shows that “TIGIT,” “type I interferon,” and “glioblastoma” are the next few years’ research Frontiers. Keyword burst analysis delineates three pivotal evolutionary stages in tumor immune escape research (Figure 10D). The pronounced bursts of “dendritic cells” and “lymphocytes” during 2009–2015 underscored foundational investigations into antigen presentation machinery and T-cell activation dynamics. Concurrently, sustained bursts of “indoleamine 2,3-dioxygenase” and “B7 family”(2009–2019) signaled the emergence of metabolic checkpoint pathways as critical regulators. The subsequent phase (2016–2021) witnessed transformative clinical advances, where bursts in “checkpoint blockade” and “PD-1 blockade correlated with therapeutic breakthroughs in immune checkpoint inhibitors, while renewed focus on “B7-H1 expression” (2015-2019) reflected its consolidation as a predictive biomarker. Current research has shifted toward tumor microenvironmental orchestration, exemplified by the burst in extracellular vesicles (2020–2022) highlighting exosome-mediated immune remodeling. Dominant ongoing bursts for tumor immune microenvironment and landscape (2023–2025) reveal accelerating adoption of spatial multi-omics and integrative biology frameworks to deconvolute immune evasion ecosystems. Notably, persistent attention to MHC class I (2010–2018) reflects enduring challenges in antigen presentation defects as core resistance mechanisms. Figure 10E categorizes keywords into 11 groups arranged chronologically, showing the most recent and prevalent keywords as ‘Immune Checkpoint Inhibitors’, ‘Sphingobacterium multivorum’, and ‘Anti PD-1 Resistance’.

Research on tumor immune evasion has sustained growth from 2009 to 2024, with no sign of abating in 2024. This reflects growing interest and attention in the field (30). Immunotherapy has become a major strategy for cancer treatment. However, tumor immune escape remains a significant challenge to the efficacy of anticancer therapies. To understand the mechanism of tumor immune escape, many targeted approaches have been explored, and some drugs have been clinically applied and achieved better efficacy (35, 36). Globally, China, the United States, and European countries are major contributors to research on tumor immune evasion. These countries’ research efforts have a clear advantage in addressing the global cancer threat. China leads in research output with 958 (52.1%) research papers published, showing the breadth and depth of its research and its great global influence. This is closely related to China’s comprehensive cancer screening and registration system and the rising cancer mortality rate (37, 38). Meanwhile, the USA and Germany have published 281(15.3%) and 114(6.2%) publications respectively, showing that the USA and Europe also have a large influence in the field of tumor immune escape. China’s cancer screening program, initiated in 1958, has significantly expanded its coverage over the past decade. This provides robust and credible primary data supporting research in the field of tumor immune escape (38). Presently, China faces a substantial cancer burden. According to the latest World Health Organization (WHO) estimates, the country accounts for 24% of global cancer incidence cases, with cancer mortality rates exceeding the global average (1, 39, 40). Consequently, the “Healthy China 2030” initiative designates cancer prevention and control as a strategic priority. Coupled with sustained investment in scientific research, these policies have enabled China to achieve significant progress in cancer prevention and treatment, while making substantial contributions to tumor immune escape research (41).

In the field of research institutions, China’s top institutions excel in output and influence. All seven institutions with the highest number of relevant publications are in China. Sun Yat-sen University leads with 72 publications and a betweenness centrality of 0.09, showing its significant position and global collaborative contribution in tumor immune evasion research. Although the University of Texas System has fewer publications, its betweenness centrality of 0.11 reflects substantial contributions to global cooperation in this field. Notably, Shandong First Medical University & Shandong Academy of Medical Sciences has rapidly risen to become a prominent player in recent years. Despite strong domestic collaborations among Chinese institutions, international cooperation remains relatively limited, which may hinder overall progress in tumor immune evasion research. Therefore, strengthening international collaborations between research institutions is crucial for accelerating global research efforts and addressing the worldwide cancer challenge.

Bibliometric analysis shows the USA and France excel in international collaboration, especially in cross - national publications. The UK, despite fewer publications, maintains strong research networks with other countries, highlighting its role in advancing global tumor immune escape research. The United States not only demonstrates strong research output in the field of tumor immune escape research, but also maintains a high proportion of multinational collaborative publications. That edge traces back to decades of steady investment by the National Cancer Institute in fostering worldwide oncology partnerships (42). Additionally, the Cancer Genome Atlas (TCGA) (43) have established accessible genomic databases that have catalyzed the formation of multinational research consortia and promoted collaborative discoveries. These collaborations facilitate knowledge sharing and enhance international synergies, enabling effective responses to global cancer challenges. Notably, low - and middle - income countries, largely due to China’s contributions, have significantly contributed to this research, helping overcome resource deficiencies and high cancer risks in these areas (44). Nevertheless, cross - border collaboration between research institutions remains limited, which may impede research progress. Enhanced global research collaboration and resource sharing could facilitate tumor immune escape research in these regions and provide more diverse perspectives and data support in the global fight against cancer.

Among journals, Frontiers in Immunology publishes the most tumor immune escape studies, far exceeding other academic journals. While Cancer Research publishes fewer articles, it has the highest average citations and impact factor (12.5), underscoring its substantial influence in this field. Among authors, Cao XT from China is the most prolific and cited. He and his team summarize the role of tumor - associated macrophages (TAMs) in promoting tumor progression and drug resistance (45), explore antibody variable region engineering applications, and discuss future antibody engineering directions to enhance cancer therapy (46).

Our bibliometric analysis shows that tumor immune escape research has evolved from focusing on classical checkpoints like PD-1/PD-L1 to exploring more complex mechanisms such as T cell exclusion, antigen presentation loss, and TME dynamics. (Table 6) Recently, emerging hotspots include combination immunotherapies, AI-assisted predictive modeling, and the cross-talk between metabolic reprogramming and the microbiome—an area gaining notable traction.

These trends have clear translational value. Insights into immune evasion are driving the development of multi-target therapeutic strategies, particularly for tumors resistant to standard immunotherapies, such as glioblastoma (GBM) and MSS colorectal cancer. Advances in single-cell profiling, spatial transcriptomics, and AI tools are further enabling precision immune phenotyping and personalized treatment planning.

At the policy level, the increasing relevance of immune escape calls for integrating immune profiling into clinical workflows and national treatment guidelines. Promoting international collaboration and investment in emerging technologies will be key to accelerating progress and improving global cancer outcomes.

Bibliometrics is crucial for processing and analyzing large-scale data to offer researchers insights into trends. Analyzing frequent keywords and subject terms can uncover changing trends and key themes, which are vital for understanding the field’s evolution. Based on the above analysis, current major hotspots focus on areas like Immune Checkpoint Inhibitors, tumor immune microenvironment, and landscape. An in-depth analysis of these research hotspots can help better understand the progress of tumor immune escape research and predict future developments in the context of current studies.

This bibliometric analysis provides a comprehensive overview of tumor immune escape research, though several methodological limitations warrant acknowledgment. First, the keyword strategy, while designed for thematic specificity, may have inadvertently excluded conceptually related topics, leading to potential omissions in the broader immuno-oncology landscape. Second, exclusive reliance on the Web of Science Core Collection—though beneficial for standardization—may underrepresent applied or interdisciplinary studies more extensively indexed in databases such as PubMed or Scopus. Third, citation-based metrics are inherently time-sensitive, often disadvantaging recent publications and reflecting academic rather than translational impact. Fourth, the exclusion of non-English publications to ensure language consistency may introduce geographic bias, potentially overlooking contributions from non-English-speaking countries. Lastly, a certain degree of subjectivity is unavoidable in the interpretation and synthesis of bibliometric findings.

The original contributions presented in the study are included in the article/. Further inquiries can be directed to the corresponding author. 1