Prognostic significance of tumor‐infiltrating lymphocytes in nondisseminated nasopharyngeal carcinoma: A large‐scale cohort study

Abstract

The American Joint Committee on Cancer (AJCC) staging system is inadequate for an accurate prognosis in nasopharyngeal carcinoma (NPC). Thus, new biomarkers are under intense investigation. Here, we investigated whether the density of TILs could predict prognosis in NPC. First, we used 1490 cases of nasopharyngeal carcinoma samples from two independent cohorts to evaluate the density and distribution of tumor-infiltrating lymphocytes (TILs). Second, in one cohort, we assessed associations between TILs and clinical outcomes in 593 randomly selected samples (defined as the training set) and validated findings in the remaining 593 samples (defined as the validation set). Furthermore, we confirmed the prognostic value of TILs in a second independent cohort of 304 cases (defined as the independent set). Based on multivariable Cox regression analysis, we also established an effective prognostic nomogram including TILs to improve accuracy in predicting disease-free survival (DFS) for patients with nondisseminated NPC. We found that high TILs in the training set were significantly associated with favorable DFS [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.28-0.58, p < 0.001], overall survival (OS, HR 0.42, 95% CI 0.27-0.64, p < 0.001), distant metastasis-free survival (DMFS, HR 0.37, 95% CI 0.23-0.58, p < 0.001) and local-regional recurrent free survival (LRRFS, HR 0.43, 95% CI 0.25-0.73, p = 0.002). Multivariate analysis showed that TILs are an independent prognostic indicator for DFS in all cohorts. In summary, this study indicated that TILs may reflect the immunological heterogeneity of NPC and could represent a new prognostic biomarker.

Establishment and Characterization of Humanized Mouse NPC-PDX Model for Testing Immunotherapy

“…Previous clinical studies have demonstrated that NPC is densely infiltrated by T cells [45], where the presence of more TIL, particularly CD3 + T cells, was associated with favorable outcomes [46,47]. In our model, TIL was detected in the humanized mice, and the percentage of intratumoral T cells was lower than those in circulation and spleen.…”

CD3+T-lymphocyte infiltration is an independent prognostic factor for advanced nasopharyngeal carcinoma

“…Abbreviations: (+ and -) are number of positive and negative patients, *P values in bold represent significant data as calculated using χ 2 or Fisher's Exact Tests, ♣ Numbers between brackets are the percentages of patients Several studies have shown the prognostic value of TIL in various types of solid tumors [9], including Head and Neck cancers [10], and more specifically, NPC [11][12][13][14], although their studies were not devoted to LA-NPC. Wang et al [13] and Almangush et al [15] have studied total TIL in NPC using H&E stained sections and found a high correlation between total TIL and disease outcome using a large cohort (1490 patients). On the other hand, Zhu et al [14], Lu et al [11], and Ono et al [12] investigated specific TIL like CD3+ and/or CD8+ TIL on survival of NPC.…”

Deep learning pathological microscopic features in endemic nasopharyngeal cancer: Prognostic value and protentional role for individual induction chemotherapy

“…13,[23][24][25] The 149 features included count ratio, nucleus perimeter, and Nucleus: Hematoxylin OD. About the count ratio, Ma et al 26 found that tumor-infiltrating lymphocytes (TILs) were independent prognostic indicators for disease-free survival (DFS) in NPC. Pathologists have observed that NPC tumor cells have obvious morphologic variations, with cells that are small and round, large and round, spindle-shaped, with or without vesicular nuclei, or mixed round and spindle-shaped.…”