TIM-3 and CEACAM1 are Prognostic Factors in Head and Neck Squamous Cell Carcinoma

Background: T-cell Immunoglobulin and Mucin domain-containing molecule-3 (TIM-3) is a new immune checkpoint molecule which plays important and complex roles in regulating immune responses and in inducing immune tolerance. TIM-3 is expressed on activated T cells and its signaling on cytotoxic T cells leads to T cell exhaustion which is mediated by carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1), another well-known molecule expressed on tumor tissues and/or tumor infiltrating lymphocytes (TILs).Methods: In the present study, we investigated TIM-3 and CEACAM1 immunohistochemical expression in 80 head and neck squamous cell carcinoma (HNSCC) specimens, linked to detailed outcome, clinic-pathological parameters. Here we reported scores and absolute counts of TIM-3+/CEACAM1+ TILs, and evaluated the expression of CEACAM1 on tumor tissues.Results: The results showed that more TIM-3+ TILs infiltration correlated with poorer overall survival (p < 0.001), as did the presence of CEACAM1 on cancer cells (p < 0.001) and CEACAM1+ TILs in tumor microenvironment (p = 0.015). Multivariate Cox regression analysis revealed that high TIM-3+ TILs may be considered as an independent prognostic factor of poor disease outcome (hazard ratio, 2.066; 95% confidence interval, 1.027–4.159; p = 0.042), as well as cancer cells expressed CEACAM1 level (hazard ratio, 5.885; 95% confidence interval, 2.832–12.230; p < 0.001).Conclusion: Our results indicate that expression of TIM-3 and CEACAM1 may represent a highly dysfunctional population of T cells. Our current findings suggest both of them were valuable predicting markers that might provide help for clinicians to design effective immunotherapeutic regimen against head and neck carcinoma.

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Neoadjuvant anti-OX40 (MEDI6469) therapy in patients with head and neck squamous cell carcinoma activates and expands antigen-specific tumor-infiltrating T cells

Nature Communications ◽

10.1038/s41467-021-21383-1 ◽

2021 ◽

Vol 12 (1) ◽

Cited By ~ 1

Author(s):

Rebekka Duhen ◽

Carmen Ballesteros-Merino ◽

Alexandra K. Frye ◽

Eric Tran ◽

Venkatesh Rajamanickam ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cells ◽

T Cell ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Primary Endpoint ◽

Locally Advanced ◽

Neck Squamous Cell Carcinoma ◽

Potential Biomarker

AbstractDespite the success of checkpoint blockade in some cancer patients, there is an unmet need to improve outcomes. Targeting alternative pathways, such as costimulatory molecules (e.g. OX40, GITR, and 4-1BB), can enhance T cell immunity in tumor-bearing hosts. Here we describe the results from a phase Ib clinical trial (NCT02274155) in which 17 patients with locally advanced head and neck squamous cell carcinoma (HNSCC) received a murine anti-human OX40 agonist antibody (MEDI6469) prior to definitive surgical resection. The primary endpoint was to determine safety and feasibility of the anti-OX40 neoadjuvant treatment. The secondary objective was to assess the effect of anti-OX40 on lymphocyte subsets in the tumor and blood. Neoadjuvant anti-OX40 was well tolerated and did not delay surgery, thus meeting the primary endpoint. Peripheral blood phenotyping data show increases in CD4+ and CD8+ T cell proliferation two weeks after anti-OX40 administration. Comparison of tumor biopsies before and after treatment reveals an increase of activated, conventional CD4+ tumor-infiltrating lymphocytes (TIL) in most patients and higher clonality by TCRβ sequencing. Analyses of CD8+ TIL show increases in tumor-antigen reactive, proliferating CD103+ CD39+ cells in 25% of patients with evaluable tumor tissue (N = 4/16), all of whom remain disease-free. These data provide evidence that anti-OX40 prior to surgery is safe and can increase activation and proliferation of CD4+ and CD8+ T cells in blood and tumor. Our work suggests that increases in the tumor-reactive CD103+ CD39+ CD8+ TIL could serve as a potential biomarker of anti-OX40 clinical activity.

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T Cell-directed Immunotherapeutic Approaches for Head and Neck Squamous Cell Carcinoma

Korean Society for Head and Neck Oncology ◽

10.21593/kjhno/2017.33.1.7 ◽

2017 ◽

Vol 33 (1) ◽

pp. 7-13

Author(s):

Yoon Seok Choi ◽

Keyword(s):

Squamous Cell Carcinoma ◽

T Cell ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma

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Expression of placenta-specific 1 and its potential for eliciting anti-tumor helper T-cell responses in head and neck squamous cell carcinoma

OncoImmunology ◽

10.1080/2162402x.2020.1856545 ◽

2020 ◽

Vol 10 (1) ◽

pp. 1856545

Author(s):

Ryusuke Hayashi ◽

Toshihiro Nagato ◽

Takumi Kumai ◽

Kenzo Ohara ◽

Mizuho Ohara ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cell ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

T Cell Responses ◽

Neck Squamous Cell Carcinoma ◽

Helper T Cell ◽

Cell Responses

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Preliminary Computed Tomography Radiomics Model for Predicting Pretreatment CD8+ T-Cell Infiltration Status for Primary Head and Neck Squamous Cell Carcinoma

Journal of Computer Assisted Tomography ◽

10.1097/rct.0000000000001149 ◽

2021 ◽

Vol Publish Ahead of Print ◽

Author(s):

Colin Y. Wang ◽

Daniel Thomas Ginat

Keyword(s):

Computed Tomography ◽

Squamous Cell Carcinoma ◽

T Cell ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Cd8 T Cell ◽

Neck Squamous Cell Carcinoma ◽

Cell Infiltration ◽

T Cell Infiltration

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Expression of the Extracellular Sulfatase SULF2 Affects Survival of Head and Neck Squamous Cell Carcinoma Patients

Frontiers in Oncology ◽

10.3389/fonc.2020.582827 ◽

2021 ◽

Vol 10 ◽

Author(s):

Yang Yang ◽

Jaeil Ahn ◽

Rekha Raghunathan ◽

Bhaskar V. Kallakury ◽

Bruce Davidson ◽

...

Keyword(s):

Overall Survival ◽

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Hpv Infection ◽

Neck Squamous Cell Carcinoma ◽

Therapeutic Interventions ◽

Tumor Tissues ◽

Significant Difference

Sulfation of heparan sulfate proteoglycans (HSPG) regulates signaling of growth factor receptors via specific interactions with the sulfate groups. 6-O-Sulfation of HSPG is an impactful modification regulated by the activities of dedicated extracellular endosulfatases. Specifically, extracellular sulfatase Sulf-2 (SULF2) removes 6-O-sulfate from HS chains, modulates affinity of carrier HSPG to their ligands, and thereby influences activity of the downstream signaling pathway. In this study, we explored the effect of SULF2 expression on HSPG sulfation and its relationship to clinical outcomes of patients with head and neck squamous cell carcinoma (HNSCC). We found a significant overexpression of SULF2 in HNSCC tumor tissues which differs by tumor location and etiology. Expression of SULF2 mRNA in tumors associated with human papillomavirus (HPV) infection was two-fold lower than in tumors associated with a history of tobacco and alcohol consumption. High SULF2 mRNA expression is significantly correlated with poor progression-free interval and overall survival of patients (n = 499). Among all HS-related enzymes, SULF2 expression had the highest hazard ratio in overall survival after adjusting for clinical characteristics. SULF2 protein expression (n = 124), determined by immunohistochemical analysis, showed a similar trend. The content of 6-O-sulfated HSPG, measured by staining with the HS3A8 antibody, was higher in adjacent mucosa compared to tumor tissue but revealed no difference based on SULF2 staining. LC-MS/MS analysis showed low abundance of N-sulfation and O-sulfation in HS but no significant difference between SULF2-positive and SULF2-negative tumors. Levels of enzymes modifying 6-O-sulfation, measured by RT-qPCR in HNSCC tumor tissues, suggest that HSPG sulfation is carried out by the co-regulated activities of multiple genes. Imbalance of the HS modifying enzymes in HNSCC tumors modifies the overall sulfation pattern, but the alteration of 6-O-sulfate is likely non-uniform and occurs in specific domains of the HS chains. These findings demonstrate that SULF2 expression correlates with survival of HNSCC patients and could potentially serve as a prognostic factor or target of therapeutic interventions.

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The circ_0032822 Promotes the Proliferation of Head and Neck Squamous Cell Carcinoma Cells Through miR-141/EF3 Signaling Axis

Frontiers in Oncology ◽

10.3389/fonc.2021.662496 ◽

2021 ◽

Vol 11 ◽

Author(s):

Shuajia Zhang ◽

Jiahui Han ◽

Jing Fu

Keyword(s):

Squamous Cell Carcinoma ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Neck Squamous Cell Carcinoma ◽

Tumor Tissues ◽

Mechanistic Analysis ◽

Repressive Effect ◽

Signaling Axis

Head and neck squamous cell carcinoma (HNSCC) refers to an epithelial malignant tumor that originates in the head and neck, and over 600,000 new cases are reported every year, However, the overall prognosis is still poor due to local recurrence and distant metastasis after surgery. The circ_0032822 has been reported upregulated in human oral squamous cell carcinoma; however, the detailed function or mechanism remains unknown. In this study, we confirmed the upregulation of circ_0032822 in HNSCC tumor tissues. Functionally, the overexpression of circ_0032822 significantly promoted the proliferation of HNSCC cell lines along with the S phase arrest and reduced apoptosis, while downregulation of circ_0032822 has the opposite effect in vitro. Mechanistic analysis showed that circ_0032822 acted as a competing endogenous RNA of miR-141 to diminish the repressive effect of miR-141 on its target E2F3. In conclusion, we demonstrated that circ_0032822 functions as a tumor oncogene in HNSCC and that its function is regulated via the miR-141/E2F3 axis.

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Inducible T cell costimulatory (ICOS) receptor agonist, GSK3359609 (GSK609) alone and in combination with pembrolizumab (pembro): Preliminary results from INDUCE-1 expansion cohorts (EC) in head and neck squamous cell carcinoma (HNSCC)

Annals of Oncology ◽

10.1093/annonc/mdz252.011 ◽

2019 ◽

Vol 30 ◽

pp. v454-v455

Author(s):

D. Rischin ◽

S.L. Groenland ◽

A.M.L. Lim ◽

J. Martin-Liberal ◽

V. Moreno ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cell ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Receptor Agonist ◽

Neck Squamous Cell Carcinoma ◽

Preliminary Results

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High stromal Foxp3-positive T cell number combined to tumor stage improved prognosis in head and neck squamous cell carcinoma

Oral Oncology ◽

10.1016/j.oraloncology.2017.02.023 ◽

2017 ◽

Vol 67 ◽

pp. 183-191 ◽

Cited By ~ 9

Author(s):

Nadège Kindt ◽

Géraldine Descamps ◽

Imelda Seminerio ◽

Justine Bellier ◽

Jérôme R. Lechien ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

T Cell ◽

Cell Carcinoma ◽

Head And Neck ◽

Squamous Cell ◽

Tumor Stage ◽

Cell Number ◽

Neck Squamous Cell Carcinoma

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Do demographics and tumour-related factors affect nodal yield at neck dissection? A retrospective cohort study

The Journal of Laryngology & Otology ◽

10.1017/s0022215116009208 ◽

2016 ◽

Vol 131 (S1) ◽

pp. S36-S40 ◽

Cited By ~ 1

Author(s):

R S Lim ◽

L Evans ◽

A P George ◽

N de Alwis ◽

P Stimpson ◽

...

Keyword(s):

Squamous Cell Carcinoma ◽

Confidence Interval ◽

Oral Cavity ◽

Cell Carcinoma ◽

Head And Neck ◽

Neck Dissection ◽

Squamous Cell ◽

Cutaneous Squamous Cell Carcinoma ◽

Neck Squamous Cell Carcinoma ◽

Nodal Yield

AbstractBackground:Nodal metastasis is an important prognostic factor in head and neck squamous cell carcinoma. This study aimed to determine the average nodal basin yield per level of neck dissection, and to investigate if age, gender, body mass index, tumour size, depth of tumour invasion and p16 status influence nodal yield.Method:A retrospective review of 185 patients with head and neck squamous cell carcinoma generated 240 neck dissection specimens.Results:The respective mean nodal yields for levels I, II, III, IV and V were 5.27, 9.43, 8.49, 7.43 and 9.02 in non-cutaneous squamous cell carcinoma patients, and 4.2, 7.57, 9.65, 4.33 and 12.29 in cutaneous squamous cell carcinoma patients. Multiple regression analysis revealed that p16-positive patients with mucosal squamous cell carcinoma yielded, on average, 2.4 more nodes than their p16-negative peers (p = 0.04, 95 per cent confidence interval = 0.116 to 4.693). This figure was 3.84 (p = 0.008, 95 per cent confidence interval = 1.070 to 6.605) for p16-positive patients with oral cavity squamous cell carcinoma.Conclusion:In mucosal squamous cell carcinoma, p16-positive status significantly influenced nodal yield, with the impact being more pronounced in oral cavity squamous cell carcinoma patients.

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