Prognostic Value of Tumor-Infiltrating CD4+ T-Cell Subpopulations in Head and Neck Cancers

Badoual, Cécile; Hans, Stéphane; Rodríguez, José Luis Villar; Peyrard, Séverine; Klein, Christophe; Agueznay, Nour El Houda; Mosseri, Véronique; Laccourreye, O.; Bruneval, Patrick; Fridman, Wolf‐Herman; Brasnu, Daniel; Tartour, Éric

doi:10.1158/1078-0432.ccr-05-1886

Cited by 538 publications

(450 citation statements)

References 52 publications

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“…Our results suggest that beyond LOH, our gene expression-based classification of OPL may provide an opportunity to refine the molecular assessment of oral cancer risk. Consistent with previous observations in HNSCC, 49–51 we found that premalignant-infiltrating T-cells and monocytes are associated with a lower oral cancer risk, suggesting an important role of these populations during oral carcinogenesis. Scattered evidence on the biology of OPL suggests the presence of an immune stimulatory environment characterized by IFN-gamma, and other pro-inflammatory cytokines and immune cells, including NK cells, macrophages and activated CD8 + T-cells.…”

Section: Discussionsupporting

confidence: 92%

Immunological and classical subtypes of oral premalignant lesions

et al. 2018

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Oral squamous cell carcinoma (OSCC) is a major cause of cancer-associated morbidity and mortality and may develop from oral premalignant lesions (OPL). An improved molecular classification of OPL may help refining prevention strategies. We identified two main OPL gene-expression subtypes, named immunological and classical, in 86 OPL (discovery dataset). A gene expression-based score was then developed to classify OPL samples from three independent datasets, including 17 (GSE30784),13 (GSE10174) and 15 (GSE85195) OPLs, into either one of the two gene-expression subtypes. Using the single sample gene set enrichment analysis, enrichment scores for immune-related pathways were different between the two OPL subtypes. In OPL from the discovery set, loss of heterozygosities (LOH) at 3p14, 17p13, TP53, 9p21 and 8p22 and miRNA gene expression profiles were analyzed. Deconvolution of the immune infiltrate was performed using the Microenvironment Cell Populations-counter tool. A multivariate analysis revealed that decreased miRNA-142-5p expression (P = 0.0484) and lower T-cell, monocytic and myeloid dendritic cells (MDC) immune infiltration (T-cells, P = 0.0196; CD8 T cells, P = 0.0129; MDC, P = 0.0481; and monocytes, P = 0.0212) were associated with oral cancer development in the immunological subtype only. In contrast, LOH at 3p14 (P = 0.0241), 17p13 (P = 0.0348) and TP53 (P = 0.004) were associated with oral cancer development in the classical subtype only. In conclusion, we identified 2 subtypes of OPLs, namely immune and classical, which may benefit from different and specific personalized prevention interventions.

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Section: Discussionsupporting

confidence: 92%

Immunological and classical subtypes of oral premalignant lesions

et al. 2018

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“…Thus, Foxp3 þ cells were analysed by immunohistochemistry in order to evaluate T regs in gastric cancer. Previous studies in human malignancies reported that the prevalence of T regs defined as a CD4 þ CD25 þ population was significantly increased in TILs compared to the normal counterparts (Woo et al, 2001;Liyanage et al, 2002;Ormandy et al, 2005;Badoual et al, 2006;Petersen et al, 2006). Furthermore, the high prevalence of CD4 þ CD25 þ T regs is closely associated with a poor prognosis in ovarian (Curiel et al, 2004) or pancreatic (Liyanage et al, 2002) cancer.…”

Section: Discussionmentioning

confidence: 96%

“…Moreover, in humans, many studies have revealed that the population of T regs in tumour-infiltrating lymphocytes (TILs) is significantly larger than in normal tissues in several malignancies (Woo et al, 2001;Liyanage et al, 2002;Ormandy et al, 2005;Badoual et al, 2006;Petersen et al, 2006). We have reported that the frequency of T regs among TILs, tumourdraining regional lymph nodes, and peripheral blood lymphocytes is higher in gastric and oesophageal cancer patients than that in their normal counterparts (Ichihara et al, 2003).…”

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confidence: 99%

Localisation pattern of Foxp3+ regulatory T cells is associated with clinical behaviour in gastric cancer

et al. 2007

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It has been reported that the population of regulatory T cells (T regs) is increased in tumour-infiltrating lymphocytes in cancer-bearing hosts. Recently, forkhead/winged helix transcription factor p3, Foxp3, is thought to be the most reliable marker of T regs. In the present study, we investigated the prevalence and localisation pattern of Foxp3 þ cells in gastric cancer (n ¼ 80) by immunohistochemistry, in relation to the clinical outcome of gastric cancer patients. Immunohistochemical staining was performed with anti-Foxp3 mAb, and Foxp3 þ cells were semiquantified. We divided all cases into two groups: Foxp3 þ -high (n ¼ 40) and Foxp3 þ -low (n ¼ 40) groups, by the median size of the population of Foxp3 þ cells. Furthermore, in terms of the localisation pattern of accumulating Foxp3 þ cells in tumours, we classified all cases into three groups: a peri-tumour group (n ¼ 30), a diffuse group (n ¼ 40), and a follicular group (n ¼ 10). As a result, although the populations of Foxp3 þ cells in stage IV were significantly larger than those in stage I (Po0.05), there was no significant difference in survival between the patients with high and low population levels of Foxp3 þ cells. However, survival in patients with a diffuse pattern of Foxp3 þ cells was significantly poorer than in those with a peritumoral pattern. In conclusion, the localisation pattern, but not the population size, of Foxp3 þ cells was significantly related to patient survival.

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“…In agreement with this hypothesis, higher numbers of tumour-infiltrating T reg were shown to be associated with poor outcome in pancreatic [25] and hepatocellular [27] carcinomas. In follicular lymphoma, head and neck, and ovarian cancer the number of infiltrating FOXP3 + immune cells has shown to be an independent prognostic factor [47][48][49]. However, studies of other tumours have led to conflicting results.…”

Section: Discussionmentioning

confidence: 99%