Prognostic Impact of Tumor‐Infiltrating Lymphocytes in Laryngeal Squamous Cell Carcinoma Patients

Abstract

Objectives/Hypothesis: Tumor-infiltrating lymphocytes (TILs) has been shown to be associated with the prognosis of many tumors, yet few studies have investigated their roles in laryngeal squamous cell carcinoma (LSCC). We aim to investigate the prognostic values of tumor-infiltrating CD3 + /CD4 + /CD8 + /Foxp3 + T-cells and neutrophils in LSCC patients that received total or partial laryngectomy.

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.…”

“…All the included studies showed a survival advantage for the cases with high CD8+ TIL. The pooled meta-analysis showed an ad- The prognostic value of CD8+ TIL was assessed in six eligible studies for inclusion in the meta-analysis [9,35,[37][38][39]41] (Figure 3). All the included studies showed a survival advantage for the cases with high CD8+ TIL.…”

“…The pooled meta-analysis showed an advantage for high CD8+ TIL density (pooled HR 0.62 (95% CI 0.4-0.97), p = 0.04, for OS, and 0.73 (95% CI 0.34-0.94), p = 0.002, for DFS). Again, in this case the evaluation of CD8+ TIL infiltration was variable: four studies considered only tumor-infiltrating CD8+ cells (CD8+ T cells counts/mm 2 of tumor area) and dichotomized the results by the median [9,35,38,39]; one study analyzed tumoral-(CD8+ T cells counts/mm 2 of tumor area) and stromal (CD8+ T cells counts/mm 2 of stromal area)-infiltrating CD8+ cells dichotomized by the median [37]; and in another one an Immunoscore was used [41], following the methodology described by Galon et al [8], considering high infiltration a score ≥ 2. The prognostic value of CD4+ and/or CD3+ TIL was assessed in four eligible studies for inclusion in the meta-analysis [9,36,37,41] (Figure 4).…”

“…Again, in this case the evaluation of CD8+ TIL infiltration was variable: four studies considered only tumor-infiltrating CD8+ cells (CD8+ T cells counts/mm 2 of tumor area) and dichotomized the results by the median [9,35,38,39]; one study analyzed tumoral-(CD8+ T cells counts/mm 2 of tumor area) and stromal (CD8+ T cells counts/mm 2 of stromal area)-infiltrating CD8+ cells dichotomized by the median [37]; and in another one an Immunoscore was used [41], following the methodology described by Galon et al [8], considering high infiltration a score ≥ 2. The prognostic value of CD4+ and/or CD3+ TIL was assessed in four eligible studies for inclusion in the meta-analysis [9,36,37,41] (Figure 4). The pooled meta-analysis showed an advantage for high CD4+ and/or CD3+ TIL (pooled HR 0.32 (95% CI 0.16-0.9), p = 0.03, for OS, and 0.23 (95% CI 0.10-0.53), p = 0.0005, for DFS).…”

“…Again, the methods of evaluation were diverse. Two studies evaluated tumor-infiltrating CD4+ cells (CD4+ T cells counts/mm 2 of tumor area) dichotomized at the median [9,36], another study stromal-infiltrating CD3+ cells (CD3+ T cells counts/mm 2 of stromal area) dichotomized at the median [37], and in another study an Immunoscore higher or equal to 2 [41]. The potential for publication bias was assessed by the visual inspection of funnel plots, since the number of studies for each meta-analysis was too small (less than 10) to allow the use of tests for funnel plot asymmetry.…”