The characterization of adaptive immunity in the tumor microenvironment of non small cell lung cancer (NSCLC) is considered of outmost importance for the stratification of patients for immunotherapeutic approaches. For this, simple, feasible, inexpensive, reproducible and pathology based methodologies are needed, such as the evaluation of routine H&E stained slides, an approach that has been recently used for the interpretation of the immune-related pathologic response in the neoadjuvant immunotherapy setting.
We aimed to determine the prognostic significance of intratumoral and peritumoral tertiary lymphoid structures (TLS), plasma cells (PCs) and necrosis in a series of 140 patients with early stage, surgically resectable NSCLC. The evaluation of TLS (3-tiered score), PCs (4-tiered score) and necrosis (absent, focal, diffuse) was performed in hematoxylin-eosin (H&E) sections from surgical specimens of pulmonary wedge resection, lobectomy or pneumonectomy. Epidemiological data have been retrieved for 76 patients so far.
In most of the tumors examined, presence of TLS and aggregates of PCs was noted (91% and 75%, respectively). The presence and density of TLS and PCs in the tumor microenvironment correlated with improved survival (p < 0.001 and p = 0.002 respectively, Kaplan-Meier). The presence of TLS also correlated positively with PC infiltrates (p < 0.001, CC = 0.644, Spearman). Importantly, all patients with diffuse large PCs aggregates (score 3) are alive for the follow-up period. On the contrary, the presence of diffuse necrosis proved to have an adverse effect on overall survival (p = 0.004, Kaplan-Meier) and showed no significant correlation with the presence of TLS and PCs.
The presence of elements of the adaptive immunity such as TLS and plasma cells is closely linked to clinical outcome in NSCLC. As plasma cell differentiation in the tumor environment correlated with the presence of TLS, this effector humoral immunity cell type might represent a surrogate marker of an effective immune response in the tumor microenvironment driven by the formation of Tertiary Lymphoid Structures.
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All authors have declared no conflicts of interest.