Tertiary lymphoid structures in lung adenocarcinoma: characteristics and related factors

Abstract

Objective Tertiary lymphoid structures (TLSs) are found in a variety of malignancies and affect the growth of tumors, but few studies have addressed their role in lung adenocarcinoma (LAC). We aimed to evaluate clinical features associated with TLSs in patients with LAC. Methods and Materials A collection of resected pulmonary nodules in patients with LAC was retrospectively analyzed. TLSs were quantified by their number per square millimeter tumor area (density) and by the degree of lymphocyte aggregation (maturity) in each case. The correlation between TLS density and maturity and clinical features was calculated. Results A total of 243 patients were selected, of whom 219 exhibited TLSs. The occurrence of TLSs was correlated with computed tomography (CT) features as follows: pure ground‐glass nodules (pGGNs) (n = 43) was associated with a lower occurrence rate than part‐solid nodules (PSNs) (n = 112) and solid nodules (SNs) were (n = 88) (p = 0.037). TLS density was correlated with age and CT features. Poisson regression showed higher TLS density in PSNs and SNs than in pGGNs (incidence rate ratio [IRR]: 3.137; 95% confidence interval [CI]: 1.35–7.27; p = 0.008 and IRR: 2.44; 95% CI: 1.02–5.85; p = 0.046, respectively). In addition, TLS density was higher in patients aged under 60 years than in those aged over 60 years (IRR: 0.605; 95% CI: 0.4–0.92; p = 0.018). The maturity of TLSs was higher in patients with higher tumor stages (p = 0.026). Conclusions We demonstrated distinct profiles of TLSs in early LAC and their correlations with CT features, age, and tumor stages, which could help understand tumor progression and management.

hoodscanR: profiling single-cell neighborhoods in spatial transcriptomics data

“…In cancer research, where the TME plays an important role in dictating therapy responses, the ability offered by hoodscanR to identify neighborhoods offers a unique perspective to investigate novel mechanisms underlying the transition of cancer cells at both transcriptomic and proteomic level. Notably, our findings from the NanoString CosMx NSCLC dataset identified cellular neighborhoods that potentially associated with the presence of TLS, which correlated with positive clinical results 11 . This capability offers the potential to contribute valuable insights into the progression of cancer, paving the way for the development of novel therapeutic strategies.…”

“…B cell neighborhoods serve as crucial sites for antibody production, contributing to the immune response against tumor cells and influencing therapeutic efficacy 10 . Furthermore, in lung cancer, the presence of tertiary lymphoid structures (TLS), characterized by highly organized T and B lymphocyte colonies within nonlymphoid tissues, has been associated with favorable clinical outcomes in non-small cell lung cancer (NSCLC) 11 . These structures, resembling secondary lymphoid organs, play an important role in regulating antitumor immune responses and are emerging as potential targets for novel therapeutic interventions.…”

Immature central tumor tertiary lymphoid structures are associated with better prognosis in non-small cell lung cancer

“…Only a few studies have examined TLS maturity in LUAD. Ren et al found that TLS maturity was higher in patients with higher tumor stages [ 22 ]. Wakasu et al suggested that mature TLSs may support antitumor immunity through lymphocyte activation [ 23 ].…”

Consolidation radiographic morphology can be an indicator of the pathological basis and prognosis of partially solid nodules

“…However, it was first noted in our study that punctate consolidation may be a pathological tertiary lymphoid structure. Tertiary lymphoid structures are clusters of lymphocyte aggregates in non-lymphatic tissues [20,21] and have been shown to participate in the antitumor immune process. Patients with tertiary lymphoid structures have been reported to benefit from long-term survival [22][23][24].…”