Expression of PD-L1 is HPV/P16-independent in oral squamous cell carcinoma

Kitichotkul, Kit; Lertprasertsuke, Nirush; Kintarak, Sompid; Pongsiriwet, Surawut; Powcharoen, Warit; Iamaroon, Anak

doi:10.1016/j.heliyon.2022.e10667

Cited by 4 publications

(3 citation statements)

References 79 publications

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“…Studies have revealed conflicting data, which may be attributed to relatively small size of cohorts, diversity of populations included in the studies, such as the broad variability of primary-tumor anatomic locations, and the associated risk factors. For instance, we did not identify a definitive correlation between HPV status and PD-L1 expression in the current or our previous studies of conjSCC, in line with findings from studies of SCCs arising from the anus, 52 oral cavity, 53 and oropharynx. 54 However, other studies have demonstrated correlations between p16 and PD-L1 expression 55 and between HPV status and PD-L1 expression in SCC of the oropharynx, 56 in which PD-L1 expression was higher among HPV+ cases and higher PD-L1 expression also correlated with longer disease-specific and overall survival.…”

Section: Discussionsupporting

confidence: 80%

Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden

Gleber-Netto,

Nagarajan,

Sagiv

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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Purpose Conjunctival squamous cell carcinoma (conjSCC) is more prevalent and aggressive in sub-Saharan African countries compared with the rest of the world. This study aims to compare the genomic, immunophenotypic, and histologic features between patients from the United States and Ethiopia, to identify etiopathogenic mechanisms and unveil potential treatment strategies. Methods We compared histologic features and mutational profiles using whole exome sequencing, high-risk human papillomavirus (HPV) status, PD-L1 expression, and tumor-infiltrating lymphocytes in conjSCC tumors of patients from Ethiopia (ETH; n = 25) and the United States (from MD Anderson [the MDA cohort]; n = 29). Genomic alterations were compared with SCCs from other anatomic sites using data from The Cancer Genome Atlas. Results Solar elastosis was seen in 78% of ETH and 10% of MDA samples. Thicker tumors had higher density of CD8+ and CD3+ cells. HPV status was similar between the cohorts (ETH = 21% and MDA = 28%). The mean tumor mutation burden (TMB) was significantly higher in conjSCC (3.01/Mb, log10) and cutaneous SCC compared other SCC subtypes. ETH samples had higher TMB compared to the MDA cohort (3.34 vs. 2.73). Mutations in genes associated with ultraviolet light (UV) signature were most frequently encountered (SBS7b = 74% and SBS7a = 72%), with higher prevalence in the ETH cohort, whereas SBS2 and SBS13 signatures were more common among MDA HPV+ conjSCCs. Conclusions Our findings suggest that UV exposure may play a major role in conjSCC, with a higher prevalence in the ETH cohort compared with the MDA cohort, where HPV also contributes.

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Section: Discussionsupporting

confidence: 80%

Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden

Gleber-Netto,

Nagarajan,

Sagiv

et al. 2024

Invest. Ophthalmol. Vis. Sci.

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“…The fraction of patients that benefit from ICB is low, with response rates of approximately 20–40% 3 , highlighting that strategies are needed to enhance the anti-tumor efficacy of ICB. Positive PD-L1 expression has been reported as a potential predictor of response to immunotherapy 4 – 6 . Although some triple-negative breast cancer (TNBC) patients have high PD-L1 expression, they are accompanied by high immunosuppression in clinical trials with PD-1 or PD-L1 blockade, as reflected by low levels of T-cell infiltration and low clinical response rates 7 – 9 .…”

Section: Introductionmentioning

confidence: 99%

“…potential predictor of response to immunotherapy [4][5][6] . Although some triple-negative breast cancer (TNBC) patients have high PD-L1 expression, they are accompanied by high immunosuppression in clinical trials with PD-1 or PD-L1 blockade, as reflected by low levels of T-cell infiltration and low clinical response rates [7][8][9] .…”

mentioning

confidence: 99%

ARIH1 activates STING-mediated T-cell activation and sensitizes tumors to immune checkpoint blockade

Liu

Cen

Wu³

et al. 2023

Nat Commun

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Despite advances in cancer treatment, immune checkpoint blockade (ICB) only achieves complete response in some patients, illustrating the need to identify resistance mechanisms. Using an ICB-insensitive tumor model, here we discover cisplatin enhances the anti-tumor effect of PD-L1 blockade and upregulates the expression of Ariadne RBR E3 ubiquitin-protein ligase 1 (ARIH1) in tumors. Arih1 overexpression promotes cytotoxic T cell infiltration, inhibits tumor growth, and potentiates PD-L1 blockade. ARIH1 mediates ubiquitination and degradation of DNA-PKcs to trigger activation of the STING pathway, which is blocked by the phospho-mimetic mutant T68E/S213D of cGAS protein. Using a high-throughput drug screen, we further identify that ACY738, less cytotoxic than cisplatin, effectively upregulates ARIH1 and activates STING signaling, sensitizing tumors to PD-L1 blockade. Our findings delineate a mechanism that tumors mediate ICB resistance through the loss of ARIH1 and ARIH1-DNA-PKcs-STING signaling and indicate that activating ARIH1 is an effective strategy to improve the efficacy of cancer immunotherapy.

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Prevalence of HPV16 L1 protein in oral biopsies: A diagnostic study from Ecuador

Zambrano,

Ramos,

Mendoza

et al. 2024

Diagnostic Microbiology and Infectious Disease

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Expression of PD-L1 is HPV/P16-independent in oral squamous cell carcinoma

Cited by 4 publications

References 79 publications

Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden

Histologic and Genomic Analysis of Conjunctival SCC in African and American Cohorts Reveal UV Light and HPV Signatures and High Tumor Mutation Burden

ARIH1 activates STING-mediated T-cell activation and sensitizes tumors to immune checkpoint blockade

Prevalence of HPV16 L1 protein in oral biopsies: A diagnostic study from Ecuador

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