Immunoscore Combining CD8, FoxP3, and CD68-Positive Cells Density and Distribution Predicts the Prognosis of Head and Neck Cancer Patients

Abstract

We assessed immune cell infiltrates to develop an immunoscore for prognosis and to investigate its correlation with the clinical data of patients with head and neck cancer. CD8, FoxP3, and CD68 markers were evaluated by immunohistochemistry in 258 carcinoma samples and positive cells were counted in stromal and intra-tumoral compartments. The RStudio software was used to assess optimal cut-offs to divide the population according to survival while the prognostic value was established by using Kaplan–Meier curves and Cox regression models for each immune marker alone and in combination. We found with univariate analysis that the infiltration of immune cells in both compartments was predictive for recurrence-free survival and overall survival. Multivariate analysis revealed that CD8+ density was an independent prognostic marker. Additionally, the combination of CD8, FoxP3, and CD68 in an immunoscore provided a significant association with overall survival (p = 0.002, HR = 9.87). Such an immunoscore stayed significant (p = 0.018, HR = 11.17) in a multivariate analysis in comparison to tumor stage and histological grade, which had lower prognostic values. Altogether, our analysis indicated that CD8, FoxP3, and CD68 immunoscore was a strong, independent, and significant prognostic marker that could be introduced into the landscape of current tools to improve the clinical management of head and neck cancer patients.

The clinicopathological significance and relapse predictive role of tumor microenvironment of intrahepatic cholangiocarcinoma after radical surgery

“…Second, the methodology still has potential limitations. Some previous studies adopted cell density to show the immune cell abundance, 36 , 37 whereas here we used positive cell ratio in mesenchyme (panCK – DAPI + ). The correlation between positive ratio and cell density shows excellent consistency (Figure S2 ), indicating that the value of positive ratio was less influenced by the cellularity of stroma.…”

Immune Cell Density Evaluation Improves the Prognostic Values of Staging and p16 in Oropharyngeal Cancer

“…Moreover, we recently proposed a new immunoscore combining CD68, CD8 and FoxP3 local distribution to identify patients with longer RFS and OS. Of note, this combination better discriminated HNSCC patients than the TNM classification [ 30 ].…”

“…Recently, an immunoscore assessing tumor-infiltrating lymphocytes (TILs) in colon cancer has been established as a new classification model, which has demonstrated better prognostic prediction than the classical TNM system [ 28 , 29 ]. Similarly, we recently identified a three-marker-based immunoscore that had a stronger prognostic performance than tumor stage [ 30 ]. Quantification of immune cells appears to be a promising approach but requires a comprehensive investigation of the immune landscape in OPSCCs.…”

The Role of Different Immunocompetent Cell Populations in the Pathogenesis of Head and Neck Cancer—Regulatory Mechanisms of Pro- and Anti-Cancer Activity and Their Impact on Immunotherapy

“…Tumour infiltrating lymphocytes (TILs) constitute a subpopulation of immunocompetent mono- and polymorphonuclear lymphocytic cells, the most important of which includes a subset of CD3 + CD4 + T helper type 1 (Th 1 ) lymphocytes, cytotoxic CD3 + CD8 + T cells (CTLs) and regulatory T lymphocytes (CD4 + CD25 + Foxp3 + T regs ). In addition to T cells, variable proportions of CD56 dim /CD16 bright activated natural killers (NK) cells, macrophages (M1/M2 phenotype macrophages, TAMs), neutrophils (N1/N2 TANs), dendritic cells (DCs), myeloid-derived suppressor cells (MDSCs), mast cells, eosinophils and basophils, and an insignificant number of B-line cells also infiltrate tumour tissue [ 49 , 50 , 51 , 55 , 56 , 57 ]. Growing evidence indicates that the immunocompetent cells in the TME may contribute to tumour initiation and progression.…”

“…Research indicates that CD4 + T helper cells, CD8 + cytotoxic T cells, NK cells, N1 neutrophils, M1 macrophages and DCs are protective against tumour growth, and that an effective interaction of these subsets is needed to protect the host against a developing tumour. Conversely, the T regs subset of CD3 + CD4 + lymphocytes, N2 neutrophils, M2 macrophages and MDSCs can promote carcinogenesis and facilitate tumour immune escape from immune destruction [ 49 , 50 , 55 , 56 , 57 ]. These interactions between immunocompetent cells, both innate (e.g., NK cells) and adaptive (e.g., CD8 + T cells) cells and the tumour itself are together referred to as immunoediting [ 49 , 51 ].…”