Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma

Nguyen, Nghia Pham Trung; Bellile, Emily L.; Thomas, Deena; McHugh, Jonathan B.; Rozek, Laura S.; Virani, Shama; Peterson, Lisa A.; Carey, Thomas E.; Walline, Heather M.; Moyer, Jeffery; Spector, Matthew E.; Perim, Daniel; Prince, Mark E.; McLean, Scott A.; Bradford, Carol R.; Taylor, Jeremy M. G.; Wolf, Gregory T.

doi:10.1002/hed.24406

Cited by 293 publications

(315 citation statements)

References 47 publications

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“…46 We observed that high levels of transcripts from one or any combination of two genes expressing immune checkpoint molecules (PD1, TIM3, TIGIT, LAG3) in HPV+, but not HPV-, HNSCC can predict patient survival after surgery. These findings require confirmation by prospective clinical studies to–we anticipate–pave the way for the development of immune-predictive biomarkers for HPV+ HNSCC patients that will ultimately lead to treatment deintensification in this patient population.…”

Section: Discussionmentioning

confidence: 81%

Treatment-naïve HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV- counterparts that has implications for immunotherapy

et al. 2018

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Cancers progress when the immune system fails to identify and eliminate malignant cells. Recognition of this, combined with advances in tumor immunology, has allowed development of therapies that induce effective anti-tumor immune responses. For incompletely-understood reasons, effective responses to immunotherapy occur in some patients and not others. Head and neck squamous cell carcinomas (HNSCC) are a common cancer type that can be divided into two subsets based on human papillomavirus (HPV) status. HPV status is a strong predictor of positive clinical outcome. Expression of exogenous viral antigens by HPV+, but not HPV-, HNSCC allows direct comparison of the immune status (immune cell presence and characteristics) between these two otherwise anatomically-similar tumors. Using TCGA data, we compared the immune landscape between HPV+ and HPV- treatment-naïve HNSCC. As compared to HPV- samples, HPV+ HNSCC exhibited a strong Th1 response characterized by increased infiltration with multiple types of immune cells and expression of their effector molecules. HPV+ HNSCC also expressed higher levels of CD39 and multiple T-cell exhaustion markers including LAG3, PD1, TIGIT, and TIM3 compared to HPV- HNSCC. Importantly, patients with higher expression of these exhaustion markers–indicative of a T-cell-inflamed tumor–correlated with markedly improved survival in HPV+, but not HPV-, HNSCC. Thus, profound differences exist between the immune landscape of HPV+ and HPV- HNSCC. These results suggest that immune checkpoint inhibitor therapy is a promising treatment strategy for HPV+ HNSCC, and that expression of immune checkpoint molecules could serve as a predictive biomarker of patient outcome in HPV+ HNSCC.

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Section: Discussionmentioning

confidence: 81%

Treatment-naïve HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV- counterparts that has implications for immunotherapy

et al. 2018

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“…Several studies have reported that the LC number is increased in the leukoplakia lesions of patients with smoking habits and in oral squamous cell carcinomas [17,18]. Similarly, HPV infection modulates the tumor immune environment as demonstrated by Nguyen et al, who reported that the number of LCs (CD1a-positive cells) is reduced in the stroma of younger oropharyngeal cancer patients with HPV infection [19].…”

Section: Introductionmentioning

confidence: 83%

Langerhans cell number is a strong and independent prognostic factor for head and neck squamous cell carcinomas

et al. 2016

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“…75 A population of CD68-positive immature myeloid cells (called myeloid-derived suppressor cells (MDSCs) that inhibit proliferation and cytokine release by T cells was found to be present in glioma 76 and squamous cell carcinoma tumors. 77 These cells can be produced by the tumor microenvironment from circulating monocytes. 78 TAMs, MDCDs, and other tumor-associated immune cells compose the leukocytic infiltrate, of which TAMs are the major contributors.…”

Section: Cd68 In Cancermentioning

confidence: 99%

CD68/macrosialin: not just a histochemical marker

Chistiakov

Killingsworth

Myasoedova

et al. 2017

Laboratory Investigation

523

330

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CD68 is a heavily glycosylated glycoprotein that is highly expressed in macrophages and other mononuclear phagocytes. Traditionally, CD68 is exploited as a valuable cytochemical marker to immunostain monocyte/macrophages in the histochemical analysis of inflamed tissues, tumor tissues, and other immunohistopathological applications. CD68 alone or in combination with other cell markers of tumor-associated macrophages showed a good predictive value as a prognostic marker of survival in cancer patients. Lowression of CD68 was found in the lymphoid cells, non-hematopoietic cells (fibroblasts, endothelial cells, etc), and tumor cells. Cell-specific CD68 expression and differentiated expression levels are determined by the complex interplay between transcription factors, regulatory transcriptional elements, and epigenetic factors. Human CD68 and its mouse ortholog macrosialin belong to the family of LAMP proteins located in the lysosomal membrane and share many structural similarities such as the presence of the LAMP-like domain. Except for a second LAMP-like domain present in LAMPs, CD68/microsialin has a highly glycosylated mucin-like domain involved in ligand binding. CD68 has been shown to bind oxLDL, phosphatidylserine, apoptotic cells and serve as a receptor for malaria sporozoite in liver infection. CD68 is mainly located in the endosomal/lysosomal compartment but can rapidly shuttle to the cell surface. However, the role of CD68 as a scavenger receptor remains to be confirmed. It seems that CD68 is not involved in binding bacterial/viral pathogens, innate, inflammatory or humoral immune responses, although it may potentially be involved in antigen processing/presentation. CD68 could be functionally important in osteoclasts since its deletion leads to reduced bone resorption capacity. The role of CD68 in atherosclerosis is contradictory.

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Tumor infiltrating lymphocytes and survival in patients with head and neck squamous cell carcinoma

Cited by 293 publications

References 47 publications

Treatment-naïve HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV- counterparts that has implications for immunotherapy

Treatment-naïve HPV+ head and neck cancers display a T-cell-inflamed phenotype distinct from their HPV- counterparts that has implications for immunotherapy

Langerhans cell number is a strong and independent prognostic factor for head and neck squamous cell carcinomas

CD68/macrosialin: not just a histochemical marker

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