Background Tertiary lymphoid structures (TLSs) within the tumor microenvironment (TME) have the function of recruiting, activating and proliferating T and B lymphocytes, and are an important source of tumor infiltrating lymphocytes (TILs), which have been shown to be related to the prognosis of many cancers.
Objective To investigate the characteristics of intra-tissue TLSs in patients with lung squamous cell carcinoma (LUSC) and their impact on prognosis.
Methods To retrospectively analyze the clinical data and pathological sections of 42 patients with pathologically confirmed LUSC who underwent radical surgical resection at the General Hospital of the People's Liberation Army and the 148th Hospital of the People's Liberation Army from 2010 to 2022, and to analyze the relationship between the TILs and TLSs features of LUSC pathology and the clinicopathological features of LUSC, as well as the prognosis of the patients.
Results Of the 42 cases, 40 were male and 2 were female, with a median age of 65 (range 50-81) years; 24 were without neoadjuvant therapy and 18 received neoadjuvant immunotherapy. QuPath software revealed that TLS contained significantly more immune cells in patients treated with neoadjuvant immunotherapy compared to those without neoadjuvant therapy. In the analysis of the relationship between TLS and clinical factors, it was found that the neoadjuvant group had a higher density of TLS, a higher density of round/elliptical TLS, and a higher maximum TLS area than the group without neoadjuvant treatment; depending on the N stage, the density of round/elliptical TLS varies, as does the density of high-cell-density TLS; higher age was associated with larger areas of maximum TLS; all differences were statistically significant (P＜0.05). Analysis of the immune response in patients with LUSC treated with neoadjuvant immunotherapy showed that patients with deepness of response ≥60% had a higher density of TILs, round/elliptical TLS, median area of TLS, low-cell-density TLS, and irregular TLS than patients with deepness of response ＜60%, and the differences were statistically significant (P＜0.05). Survival analysis of 22 patients in the group without neoadjuvant therapy showed that higher density of round/elliptical TLS had a relatively better prognosis compared to the lower density group (median overall survival mOS: 53.5 months vs 25.0 months, P=0.069), the group with higher area of maximum TLS had a relatively better prognosis compared with the group with lower area (mOS: 50.0 months vs 25.0 months, P=0.074), with a P value close to 0.05.
Conclusion Those who received neoadjuvant immunotherapy had greater characteristics of TLS than those who did not, and those who responded well to immunotherapy had greater characteristics of TLS than those who responded poorly, and higher density of TLS, higher density of rounded/elliptical TLS, and a larger area of maximum TLS may be indicative of a favorable prognosis.
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