Why EGFR-mutant NSCLC TME matters NSCLC is the most common type of lung cancer, and approximately 44-50% of Asian patients harbor EGFR mutations. The tumor microenvironment (TME) - the cellular and molecular context surrounding tumor cells - plays a critical role in determining disease progression, TKI resistance, and response to immunotherapy.
Bibliometrics as a research tool Bibliometric analysis uses quantitative methods to map the volume, collaboration patterns, topic trends, and influential outputs across a scientific field. Applied to EGFR-mutant NSCLC TME research, it reveals how the field has evolved and where current scientific attention is concentrated.
Study scope This Frontiers in Immunology (2025) study analyzed 227 publications from the Web of Science Core Collection (WoSCC) published between 2014 and 2023, covering all articles related to the TME in NSCLC with EGFR mutation.
Analytical framework The analysis covered country/institutional collaboration networks, author productivity, journal distribution, citation patterns, keyword co-occurrence, and burst analysis to identify emerging research themes.
Global research output The 227 included papers came from 102 countries and 1,179 institutions, reflecting truly global scientific engagement with EGFR-mutant NSCLC TME biology.
International collaboration networks Network analysis showed that the strongest international collaboration link was between the USA and China (link strength = 13), followed by USA-South Korea (LS = 3) and USA-Japan (LS = 3). The USA-China partnership dominates this research domain.
Author productivity A total of 2,267 authors contributed to the 227 articles. The analysis identified the most prolific and most-cited authors, revealing a core group of researchers whose work has disproportionately shaped the field.
Journal landscape 112 journals published research in this area. Frontiers in Oncology was the most prolific single journal with 16 papers (14.3% of total), reflecting this journal's broad open-access coverage of translational oncology research.
Co-citation network Analysis of 7,964 co-cited references identified the foundational papers whose findings most strongly underpin subsequent research. Highly co-cited works typically establish key concepts or provide landmark clinical data referenced by multiple later studies.
Centrality of EGFR as a concept The keyword 'EGFR' had the highest centrality measure (C = 0.31) among all keywords analyzed and appeared earliest in the literature, confirming its role as the foundational concept around which this research field is organized.
Citation hotspots Papers addressing TKI resistance mechanisms, TME immune composition in EGFR-mutant tumors, and the immunosuppressive features distinguishing EGFR-mutant from EGFR wild-type tumors were among the most frequently cited.
Research evolution Citation pattern analysis revealed a shift from early basic science characterization of EGFR biology toward later translational work on TME immune landscape and therapeutic implications, tracking the evolution of clinical practice.
Burst keywords in 2022-2023 Keyword burst analysis identified the most rapidly growing research themes in the most recent years: 'immunotherapy,' 'mechanism,' 'lung neoplasms,' 'T cells,' and 'multicenter.' These represent the current frontier of the field.
Immunotherapy as the key emerging theme The burst of 'immunotherapy' as a keyword reflects the clinical challenge of using immune checkpoint inhibitors in EGFR-mutant NSCLC patients, where ICIs have shown limited efficacy compared to EGFR wild-type disease.
T cell biology focus The emergence of 'T cells' as a burst keyword reflects growing interest in understanding how EGFR mutations affect T cell infiltration, exhaustion, and effector function within the TME - a mechanistic understanding needed to improve immunotherapy outcomes.
Multicenter trial growth The emergence of 'multicenter' reflects a maturing field moving from single-institution basic or retrospective studies toward larger collaborative trials examining TME-related predictive biomarkers and therapeutic strategies.
EGFR mutations and immune exclusion A major finding synthesized from the literature is that EGFR mutations are associated with a relatively immune-cold TME characterized by lower CD8+ T cell infiltration and higher regulatory T cell and myeloid-derived suppressor cell populations compared to EGFR wild-type tumors.
PD-L1 expression nuances EGFR-mutant tumors often express moderate PD-L1 levels, but this does not translate into robust ICI responses. The discordance suggests that EGFR-driven oncogenic signaling actively suppresses T cell function beyond what PD-L1 expression alone predicts.
EGFR-driven immunosuppressive pathways EGFR signaling activates downstream pathways including STAT3 and NF-kB that promote immunosuppressive cytokine production, creating a TME that actively excludes and exhausts tumor-reactive immune cells.
Resistance mechanism insights After EGFR-TKI treatment, the TME can undergo changes that either restore or further suppress anti-tumor immunity. Understanding these dynamic TME changes is critical for designing effective combination strategies.
ICI combination strategies The bibliometric analysis identifies overcoming EGFR-driven immunosuppression to enable effective immunotherapy as the central unmet need. Rational combinations of EGFR-TKIs with immunomodulatory agents or next-generation immunotherapy approaches represent the primary therapeutic frontier.
Biomarker discovery Identifying reliable predictive biomarkers for ICI efficacy in EGFR-mutant NSCLC - beyond PD-L1 and tumor mutational burden - is highlighted as a critical research priority, potentially emerging from TME profiling with multi-omics approaches.
Resistance mechanism studies As the burst analysis shows growing interest in mechanisms of treatment failure, elucidating how the TME evolves during and after TKI therapy is expected to guide next-line treatment sequencing strategies.
Global research capacity The strong USA-China collaboration network suggests that future multicenter clinical studies with diverse patient populations could generate the large-scale evidence needed to resolve open questions about TME biomarkers and combination therapy efficacy.