A role for the immune system in advanced laryngeal cancer

Abstract

To investigate the role of the altered activation of the immune system in the prognosis of patients affected by laryngeal squamous cell carcinoma (LSCC). We analyzed 56 patients with advanced LSCC divided into two groups according to their prognosis: the first group relapsed within 24 months after treatment, the second group had no evidence of disease at 2 years. The presence of stromal tumor infiltrating lymphocytes (TILs) at the tumor-host border was investigated. In 43 patients we evaluated the expression of 395 genes related to immune system activation through a next generation sequencing panel. Priority-LASSO models and clustering analyses were integrated with multivariate Cox proportional hazard modeling to identify independent genes associated with relapse and estimate hazard ratios in relation to gene expression and TILs. TILs and the expression of genes related with immune system activation (FCGR1A, IFNA17, FCRLA, NCR3, KREMEN1, CD14, CD3G, CD19, CD20 and CD79A) were significantly associated with prognostic factors or disease specific survival. In patients with lymph node metastases and advanced T stage (pT4), the expression of other genes was altered. Low TILs count was highly associated with relapse within 2 years (p < 0.001). Low TILs and altered expression of specific genes associated with tumor-immune systems interactions emerged as independent risk factors, associated to poor prognosis and relapse within 2 years in advanced LSCC. Evaluation of patients’ immune profile could be useful for prognosis and future therapeutic approaches towards personalized therapy.

Tumor-Infiltrating Lymphocytes in the Tumor Microenvironment of Laryngeal Squamous Cell Carcinoma: Systematic Review and Meta-Analysis

“…Of these, seven were excluded because they did not report the outcome of LSCC separately from other locations of HNSCC [12,[15][16][17][18][19][20], eight because no HRs were available [21][22][23][24][25][26][27][28][29], one study because they reported outcome in terms of local control [30], one study that evaluated Il-12R expression on tumor cells [31], and one study that evaluated lymphocytes in peripheral blood [32]. This left 11 studies for the analysis (Figure 1) [9,[33][34][35][36][37][38][39][40][41][42]. All the studies included in this review were retrospective.…”

“…Tagliabue et al, 2020 [40] Low TIL and altered expression of specific genes associated with tumor-immune systems interactions emerged as independent risk factors, associated with poor prognosis and relapse within 2 years in advanced laryngeal squamous cell carcinoma. The prognostic value of TILs in HE-stained sections was assessed in five eligible studies for inclusion in the meta-analysis [33,34,38,40,42], although not all the studies included the results of DFS and OS (Figure 2). These five studies analyzed the infiltration by TIL of the tumor stroma in resected specimens.…”

“…Three studies defined a high stromal infiltration by TIL when it was higher or equal to 30% [33,34,42]. Another study defined a high stromal infiltration by TIL when it was higher or equal to 5% [40], and another one defined the stromal infiltration by TIL as a continuous variable (increments of 10%) [38]. The prognostic value of CD8+ TIL was assessed in six eligible studies for inclusion in the meta-analysis [9,35,37-39,41] (Figure 3).…”

Identification of Autophagy- and Ferroptosis-Related lncRNAs Functioned through Immune-Related Pathways in Head and Neck Squamous Carcinoma

“…Among these, PLAC8 were found to regulate autophagy-related functions in a variety of cancers [51,52]. In addition, numerous DEGs were reported to be involved in the proliferation and differentiation of immune cells and could regulate immune functions, including CD226, IRF4, LY9, MS4A1, TBX21, TNFRSF17, FCRLA, and SLAMF6 [45,[53][54][55][56][57][58].…”

“…Life 2021, 11, x FOR PEER REVIEW 9 of 18 in a variety of cancers [51,52]. In addition, numerous DEGs were reported to be involved in the proliferation and differentiation of immune cells and could regulate immune functions, including CD226, IRF4, LY9, MS4A1, TBX21, TNFRSF17, FCRLA, and SLAMF6 [45,[53][54][55][56][57][58]. To further characterize and understand the biological insights of these DEGs, we performed gene ontology (GO) and KEGG analysis.…”