Analysis of the geographical distribution of publications

The global landscape of T cell-based immunotherapy for cancer treatment demonstrates a significant and growing international commitment, with an increasing volume of research outputs and widespread collaboration across borders. As shown in Fig. 1A, the annual and cumulative publication outputs have consistently risen from 2000 to 2024, highlighting not only an expanding scientific interest in the field but also the substantial advancements in the development of T cell therapies. This surge in publications signifies the growing recognition of T cell-based immunotherapy in PC as a transformative approach to cancer treatment, with contributions from diverse research centers around the world. The USA has long been at the forefront of T cell-based immunotherapy in PC research, as evidenced in Table 1, where the USA accounts for approximately 35% of the total publications. This leadership is further reflected in Fig. 2B, where the USA ranks highest in terms of the H-index—a metric that integrates both publication volume and citation impact. While the USA maintains its dominant role in the field, other nations, notably China and Germany, have emerged as significant contributors, ranking second and third in publication volume, respectively. The geographical distribution of citations, depicted in Fig. 2D, reveals a nuanced landscape: although the USA leads in total citations, countries such as France, the Netherlands, and Australia outperform in terms of average citations per publication. This suggests a shift toward more specialized, high-impact research in these regions, with Australia, in particular, standing out for its applied research focus in clinically translatable studies. The varying citation patterns underscore the different research priorities across regions, with North America contributing foundational scientific studies and Europe and Oceania focusing on clinical applications and translational innovations.

The extensive international collaboration network plays a pivotal role in accelerating progress in this field. Figure 2E, F highlights the strong collaborative ties between research hubs in the USA, China, and Europe, demonstrating the interconnectedness of the global research community. These collaborations facilitate the exchange of knowledge, resources, and methodologies, fostering a collective effort to overcome the challenges of developing effective T cell therapies. This interconnected network is essential not only for advancing scientific knowledge but also for ensuring the integration of diverse perspectives that enrich the research process and enhance the global impact of discoveries. In Fig. 3C, at the institutional level, leading research centers, such as Helmholtz Association, the University of California System, and UTMD Anderson Cancer Center, continue to dominate both in terms of publication output and collaborative engagement. As illustrated in Fig. 4A, B, these institutions not only produce a significant proportion of global research but also serve as key hubs for international collaboration. Their collaborations with institutions across Europe, Asia, and other regions amplify the global reach and impact of their work, further accelerating advancements in T cell immunotherapy.

In conclusion, the bibliometric analysis of T cell-based immunotherapy in PC research underscores the dynamic and highly collaborative nature of the field. While the USA, China, and Germany are the primary contributors in terms of publication volume, countries such as France, Italy, and Australia stand out for their higher citation impact, reflecting the diversity of research approaches and focuses across regions. The expanding network of international collaborations remains a cornerstone of progress in this field, ensuring that research efforts are enhanced by a variety of perspectives and expertise. As the field of cancer immunotherapy continues to evolve, it will be shaped by the collective contributions of researchers worldwide, driven by a shared commitment to improving patient outcomes through innovative therapies and cutting-edge research.

Analysis of journals, and studies

The global landscape of T cell-based immunotherapy in PC for cancer treatment reflects a rapidly evolving and highly specialized research field, with a clear concentration of publications in influential journals. As shown in Fig. 5A, journals such as Cancer Immunology Immunotherapy, Cancers, and Clinical Cancer Research dominate, acting as primary platforms for disseminating cutting-edge research. Other prominent journals, including Frontiers in Immunology and Journal for Immunotherapy of Cancer, reflect the growing interest in immunotherapy as a central focus of cancer treatment. The time-series data in Fig. 5B highlights the consistent rise in journal output, with publications in key journals such as Cancer Immunology Immunotherapy showing marked growth. This trend underscores the increasing prominence of T cell immunotherapy as an area of both academic and clinical interest. Bradford’s Law analysis, presented in Fig. 5C and Table 3, further illustrates the structure of knowledge dissemination, with a small number of core journals responsible for the majority of publications. This concentration suggests the establishment of a specialized and influential research community that drives the future of T cell immunotherapy. The subject categorization of T cell immunotherapy research further emphasizes its strong foundation in oncology. As shown in Table 5, Oncology stands as the leading subject category, with Immunology following closely behind, reflecting the critical intersection between cancer research and immune system therapies. Complementary fields such as Medicine, Research & Experimental, Biochemistry & Molecular Biology, and Gastroenterology & Hepatology indicate the interdisciplinary nature of the research, bridging basic science and clinical application. This diversity highlights the multifaceted approach to T cell-based immunotherapy in PC, spanning from fundamental immunological studies to clinical translational applications aimed at improving cancer treatment outcomes.

Citation network analysis, represented in Fig. 6A, provides a comprehensive view of the intellectual structure of the field, with dense interconnections among influential studies that have shaped the direction of T cell immunotherapy. The citation bursts shown in Fig. 6B identify key papers that have sparked significant attention during specific periods, marking major breakthroughs in the field. These citation surges reflect the transformative nature of research advancements, which have led to paradigm shifts in the development of new therapies and approaches to cancer treatment. Funding has played a pivotal role in advancing T cell immunotherapy, with major funding agencies such as the United States Department of Health and Human Services (HHS) and the National Institutes of Health (NIH) providing substantial support, as shown in Table 6. International agencies, including the National Natural Science Foundation of China (NSFC) and the European Research Council (ERC), also contribute significantly, reflecting the global commitment to advancing T cell-based immunotherapies. The support from these funding bodies is crucial for driving continued progress in the field and ensuring the translation of research findings into clinical applications.

In conclusion, the bibliometric analysis of T cell-based immunotherapy in PC for cancer treatment reveals a well-established, interdisciplinary research domain. The concentration of research in high-impact journals, the ongoing rise in publication output, and the support from leading funding agencies point to a rapidly advancing field poised for significant clinical impact. As research continues to evolve, these insights provide valuable guidance for future directions and emerging opportunities in the development of T cell therapies for cancer treatment.

Analysis of research hotspots

The landscape of T cell-based immunotherapy for PC treatment has evolved significantly, as highlighted by dynamic keyword clustering, citation bursts, and temporal shifts in research focus. The keyword co-occurrence network (Fig. 8A) reveals strong interconnections between core research areas such as “T cells,” “cancer immunotherapy,” and the “tumor microenvironment,” suggesting an integrated approach to cancer treatment. Cluster decomposition analysis (Fig. 8B) identifies distinct and emerging research domains, while the timeline visualization (Fig. 8C) tracks the evolving nature of these areas over time. Citation burst analysis (Fig. 9) further highlights high-impact topics, including “pancreatic cancer” and “immunotherapy,” marking them as central to future research trajectories.

T cell immunotherapy: advancements and optimization

T cell-based immunotherapy in PC has solidified its position as a cornerstone of cancer treatment, reflected in its dominance in keyword rankings and citation bursts (Figs. 8 and 9). Immunotherapy leverages the immune system, particularly T cells, to target and eliminate cancer cells with precision (Oliveira and Wu 2023). This approach has gained widespread attention due to its potential to significantly improve cancer treatment outcomes, particularly for hard-to-treat cancers.

Recent advancements focus on optimizing T cell activation, expansion, and targeting (Perica et al. 2014; Wu et al. 2020a). T cells, when activated appropriately, have the capacity to recognize and attack tumor cells presenting specific antigens. However, their therapeutic potential is often hindered by factors such as the immunosuppressive TME and tumor heterogeneity (Falcomatà et al. 2023; Dagogo-Jack and Shaw 2018). Therefore, current research aims to enhance the effectiveness of T cells by engineering them to better recognize tumor markers and by expanding them ex vivo before reinfusion. The increasing prominence of terms such as “T cell receptor” and “adoptive immunotherapy” underscores the growing focus on these strategies. Adoptive T cell therapy, particularly Chimeric Antigen Receptor T cell (CAR-T) therapy, has already achieved remarkable success in treating hematologic cancers like leukemia and lymphoma (Zhang et al. 2022; Hamilton et al. 2024; Leick et al. 2022). These approaches are increasingly being explored in solid tumors, where barriers such as limited intratumoral trafficking and TME-mediated immunosuppression remain major hurdles. Continued advances in CAR-T engineering and refinements to adoptive T-cell strategies point to a future in which T-cell immunotherapy could become a broadly effective option across multiple cancer types.

PC-specific clinical efforts have tested engineered T-cell therapies. In a Phase I study of transient mRNA mesothelin-directed CAR-T cells, 2 of 6 patients with chemotherapy-refractory PC achieved stable disease with marked metabolic responses and acceptable safety (Beatty et al. 2018). A pilot trial evaluating co-infusion of mesothelin- and CD19-targeted CAR-T cells reported feasibility and disease stabilization in 1 of 3 metastatic PC patients (Ko et al. 2020). For TCR therapy, a NEJM case report documented objective regression of metastatic PC following infusion of KRAS^G12D-specific TCR-engineered T cells (Simnica and Kobold 2022). For TIL therapy, the field has reached a regulatory milestone: in 2024, the US FDA approved lifileucel (Amtagvi) for unresectable or metastatic melanoma following prior PD-1 therapy. While not yet standard in PC, TIL-based therapy is under prospective evaluation in PC cohorts within Phase I/II trials (e.g., NCT03935893; NCT05098197), although definitive efficacy signals remain pending. Together, these PC-relevant clinical data substantiate the approach’s clinical relevance while underscoring the need for larger, dedicated trials to define patient selection, dosing, and risk–benefit profiles.

Tumor microenvironment (TME) and immunosuppressive mechanisms

The TME plays a critical role in the success or failure of T cell-based therapies, as reflected by its continued prominence in both network analysis (Fig. 8A, B) and citation bursts (Fig. 9). The TME is composed of a variety of components-including immune cells, stromal cells, and extracellular matrix elements-that not only support tumor growth but also create an immunosuppressive environment (Wu et al. 2022, 2020b). This immune suppression can inhibit the ability of T cells to effectively target and destroy cancer cells.

To improve T cell therapy outcomes, significant research is focused on overcoming the immunosuppressive TME. Strategies aimed at modifying the TME include targeting immune checkpoint inhibitors like PD-1 and CTLA-4 (Kumagai et al. 2022; Marangoni et al. 2021). These immune checkpoints act as “brakes” on the immune system, and blocking them has led to major breakthroughs in cancer treatment, particularly for melanoma and non-small cell lung cancer (Kleffel et al. 2015; Cheng et al. 2024). The combination of immune checkpoint inhibitors with T cell therapies is showing great promise, enabling T cells to overcome TME-induced suppression. The growing presence of keywords such as “immune checkpoints” and “tumor microenvironment” signifies an increasing recognition of the need to address the TME in the development of effective cancer immunotherapies. Additionally, other novel approaches, including the use of engineered nanoparticles and oncolytic viruses to modify the TME, are being explored to enhance immune responses and improve treatment efficacy (Liu et al. 2023). These innovations underscore the importance of addressing the TME as a central challenge in T cell-based cancer therapies.

Precision immunotherapy: tumor antigens and personalized approaches

The identification and targeting of tumor antigens are another burgeoning area in T cell-based immunotherapy in PC, as evidenced by the growing prominence of terms such as “tumor antigens,” “monoclonal antibodies,” and “personalized therapy” (Figs. 8 and 9). Tumor-specific antigens are proteins or molecules expressed predominantly on cancer cells, making them ideal targets for immune-mediated destruction (Fan et al. 2023). Precision immunotherapy seeks to harness these tumor-specific markers to design more targeted and effective treatments, thereby minimizing off-target effects and improving therapeutic outcomes.

Monoclonal antibodies play a key role in precision immunotherapy, enhancing T cell targeting by either blocking immune suppressive signals (such as immune checkpoint inhibitors) or directly targeting tumor antigens (Zhao et al. 2021). The growing interest in “monoclonal antibodies” and “personalized therapy” in the keyword rankings underscores the importance of this strategy. For example, engineered T cells, such as CAR-T cells, can be designed to recognize specific tumor antigens, offering a highly targeted treatment option (Hong et al. 2020; Tieu et al. 2024). Additionally, the combination of monoclonal antibodies with T cell therapies is a promising avenue for improving both the specificity and efficacy of cancer treatments. Research is increasingly focused on identifying novel tumor antigens that could serve as targets for immunotherapy. As these antigens are identified and validated, the potential for personalized T cell-based therapies to treat a broad range of cancers will continue to expand.

Future research trends

The future of T cell-based immunotherapy for PC treatment is set to undergo a transformation, with rapid advancements in immunology, bioengineering, and precision medicine. The insights drawn from keyword networks (Fig. 8A), cluster analyses (Fig. 8B), and citation burst data (Fig. 9) suggest that the next phase of cancer immunotherapy will focus on a convergence of innovative technologies and approaches. These include the enhancement of T cell therapies through novel modifications, the integration of immune-modulating agents, and the development of patient-specific, personalized therapies. These trends highlight a paradigm shift toward more adaptive, biologically integrated, and precisely targeted therapeutic strategies aimed at improving cancer treatment outcomes.

T cell modulation and enhancement technologies

A key focus in the future of T cell immunotherapy is the development of novel T cell modulation technologies designed to optimize T cell functionality, enhance their persistence, and overcome the challenges posed by immune evasion mechanisms in tumors. The increasing prominence of terms such as “T cell receptor”, “adoptive immunotherapy”, and “tumor antigens” in the keyword network (Fig. 8A, B, and Table 7) signals the continued focus on improving the specificity, activity, and durability of T cell therapies.

Advances in gene editing technologies, such as CRISPR-Cas9, are enabling the creation of highly specialized T cells that can bypass the immunosuppressive effects of the TME (Schmidt et al. 2022; Chen et al. 2021). By genetically modifying T cells, scientists can enhance their tumor-targeting abilities, increase their resistance to immune checkpoint inhibitors, and improve their persistence in the body, thus maximizing their therapeutic potential. This is particularly critical for treating solid tumors, which are known for being more resistant to conventional T cell therapies.

Further innovations in TCR engineering will also play a crucial role (Baulu et al. 2023; Zhao et al. 2022; Isshiki et al. 2025). Researchers are working to enhance the ability of T cells to recognize tumor-specific antigens with higher precision. In parallel, immune modulation strategies aimed at overcoming the suppressive effects of regulatory T cells (Tregs) and other components of the TME are gaining traction (Zhang et al. 2024; Goverman 2021). The ability to “reprogram” the TME to make it more conducive to T cell activation is essential for improving the outcomes of T cell therapies. The use of immune checkpoint inhibitors like anti-PD-1 and anti-CTLA-4 has already proven successful in boosting T cell responses, and combining these therapies with engineered T cells may become a standard strategy to enhance cancer immunotherapy (Kumagai et al. 2022). As “antitumor immunity” continues to gain recognition in citation bursts (Fig. 9), combining immune checkpoint blockade with T cell modulation will likely be a central approach in future therapeutic regimens.

Integration of immune modulation agents and cancer vaccines

Another key trend in the evolution of T cell immunotherapy is the integration of immune modulation agents and cancer vaccines with T cell-based treatments. As shown in the network and citation burst data (Fig. 8A, B, and Table 7), the combination of T cell therapies with other immune-enhancing agents such as monoclonal antibodies, tumor vaccines, and adjuvants will drive the next wave of innovation in cancer immunotherapy. The integration of these therapies aims to stimulate a robust and targeted immune response against cancer cells, while minimizing systemic side effects and improving the overall efficacy of treatment.

The development of cancer vaccines that specifically target tumor antigens and stimulate T cells is expected to become a prominent area of research (Waldman et al. 2020; Sethna et al. 2025). These vaccines can help train the immune system to recognize cancer-specific markers, triggering a powerful immune response that targets and eliminates cancer cells. Combining vaccines with immune checkpoint inhibitors can further enhance the activity of T cells, providing a synergistic effect that is likely to improve treatment outcomes. Moreover, adjuvants-substances that enhance the immune response to a vaccine-will play an important role in improving the potency of cancer vaccines.

Personalized and precision immunotherapy

Personalized medicine is the future of T cell-based immunotherapy in PC, as it aims to design treatment strategies tailored to the unique genetic and molecular profile of each patient’s tumor. The sustained prominence of terms such as “personalized therapy”, “tumor microenvironment”, and “targeted therapies” in keyword rankings (Fig. 8A, B, and Table 7) signals a shift toward highly individualized therapeutic regimens. Research in this area will focus on profiling individual tumors to identify specific mutations, biomarkers, and antigens that can be targeted by T cell therapies (Cao et al. 2022).

Next-generation sequencing (NGS) and liquid biopsy technologies will be at the forefront of this transformation, enabling the rapid identification of tumor-specific mutations and the design of customized therapies that target those alterations (Mosele et al. 2024; Loy et al. 2024). By leveraging artificial intelligence (AI) and machine learning, oncologists will be able to predict which T cell therapy regimens are most likely to be effective based on the individual patient’s tumor characteristics (Perez-Lopez et al. 2024; Keyl et al. 2025). These AI-driven platforms will analyze vast amounts of clinical and genetic data to recommend the optimal treatment strategies, enhancing both efficacy and safety.

Epigenetic modulation to enhance T-cell-based immunotherapy

Epigenetic regulators shape tumor antigenicity and T-cell fate. Dual or selective EZH1/EZH2 inhibition can reprogram tumors toward an immunogenic phenotype and potentiate CAR-/TCR-engineered T cells; in parallel, transient EZH2 inhibition during ex vivo expansion preserves T-cell stemness and improves ACT efficacy, including in combination with PD-1 blockade (Porazzi et al. 2025; Hou et al. 2025). These data nominate epigenetic–immunotherapy combinations as testable strategies in PC to overcome poor antigenicity, stromal exclusion, and myeloid-dominant suppression.

Broader clinical context: supportive care

Although liver and peritoneal dissemination predominate in PC, bone metastases-while relatively uncommon-can be clinically devastating and under-recognized. Case-based syntheses indicate that bone-targeted agents such as zoledronic acid may warrant exploration for skeletal protection and symptom control in this population, extrapolating from broader oncology experience (Argentiero et al. 2019). These agents are not standard of care in PC, and prospective PC-specific data remain limited; nevertheless, integrating bone health assessment and considering anti-resorptive strategies in selected patients may open supportive avenues within comprehensive care pathways. Future work should clarify patient selection, dosing schedules, and risk–benefit profiles in PC cohorts (Sanford et al. 2013).

The future of T-cell-based immunotherapy for cancer treatment is set to undergo significant advancements, with several key areas driving this transformation. Research will focus on enhancing T-cell therapies through novel modulation technologies designed to optimize T-cell functionality, increase their persistence, and overcome immune evasion mechanisms employed by tumors. The integration of immune-modulating agents, such as immune checkpoint inhibitors and cancer vaccines, will further enhance the overall efficacy of T-cell therapies by promoting more robust and targeted immune responses (Peng et al. 2025). At the same time, personalized and precision immunotherapy will allow treatments to be tailored to individual tumor profiles, utilizing advanced technologies like next-generation sequencing, liquid biopsy, and artificial intelligence to optimize therapy selection (Basiri 2023). Additionally, epigenetic modulation will emerge as a promising approach to enhance T-cell activity, potentially improving outcomes in challenging cancers. Moreover, broader clinical contexts will focus on improving patient quality of life by exploring supportive care strategies that complement cancer treatments (Villanueva et al. 2020). Collectively, these research directions highlight a paradigm shift toward more adaptive, biologically integrated, and precisely targeted therapeutic strategies that will not only improve cancer treatment outcomes but also move beyond conventional, one-size-fits-all approaches, offering renewed hope for cancer patients.

Limitations of this study

This bibliometric analysis offers valuable insights into the evolving landscape of T cell-based immunotherapy for PC. However, several limitations must be acknowledged. A fundamental challenge remains the incomplete understanding of how engineered T cells interact with the highly immunosuppressive pancreatic tumor microenvironment. The precise molecular mechanisms regulating T cell infiltration, persistence, and functional exhaustion within these tumors are not yet fully elucidated, posing a barrier to the rational design of more effective and durable immunotherapies. Bridging these gaps is essential for optimizing next-generation strategies that enhance antitumor immunity while overcoming resistance mechanisms.

Methodologically, this study is subject to potential selection biases due to database constraints and language restrictions. The exclusion of key repositories such as PubMed, Cochrane, and Embase, as well as non-English literature, may have limited the comprehensiveness of the analysis. Although Sect. 3.5 briefly acknowledges these issues, the study does not include a detailed comparison of publication counts across databases or a more in-depth exploration of their impact, which could have further clarified the representativeness of the findings. Additionally, reliance on citation frequency as a primary metric may undervalue recently published, high-impact studies that have not yet accumulated extensive citations, potentially skewed bibliometric trends and underrepresenting emerging innovations in T cell therapies for PC. Potential tool-specific biases introduced by VOSviewer and CiteSpace were not explicitly discussed. The algorithms and weighting schemes used by these visualization tools may influence clustering patterns and network representations, but the current analysis only addresses general methodological limitations without detailing such tool-related constraints. Furthermore, the visualization and clustering results may be influenced by the inherent algorithms and weighting schemes applied in tools such as VOSviewer and CiteSpace, which could introduce additional bias.

To provide a more comprehensive and representative analysis, future studies should integrate a broader range of databases and multilingual sources. Moreover, refining bibliometric methodologies to account for emerging but under-cited research could yield a more accurate depiction of advancements in the field. Future efforts should also explicitly address potential biases introduced by visualization tools such as VOSviewer and CiteSpace, ensuring that algorithmic and weighting-related limitations are transparently acknowledged. Such efforts will be instrumental in accelerating the development of engineered T cell therapies with enhanced tumor infiltration, resistance to immunosuppressive signaling, and improved clinical efficacy, ultimately contributing to more effective treatment strategies for PC.