Association of PD-L1 expression in oral squamous cell carcinoma with smoking, sex, and p53 expression

Ahmadi, Navid; Gao, Kan; Chia, Noel; Kwon, Min Sung; Gupta, Ruta; Clark, Jonathan

doi:10.1016/j.oooo.2019.07.008

Cited by 22 publications

(18 citation statements)

References 30 publications

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“…In accordance with others, we noted a significant association between the absence of smoking [7], female gender, and absence of comorbidities [11]. The relatively rich inflammatory milieu in the tongue (compared to the larynx) may explain the significantly higher CPS we have demonstrated in tongue carcinoma [13].…”

Section: Discussionsupporting

confidence: 92%

“…Moreover, different histopathological scenarios, including heterogeneity of PD-L1 expression both within and between tumor sites, is a well-documented phenomenon. All of the above may compromise the predictive power of PD-L1 and the current literature in this regard is inconsistent [7], precluding firm conclusions. Our main hypothesis is that heterogenic PD-L1 tissue expression in HNSCC may attribute to CPS category mismatch in biopsies versus whole carcinoma analyses, affecting treatment decisions.…”

Section: Introductionmentioning

confidence: 98%

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Spatial Intratumoral Heterogeneity Expression of PD-L1 Antigen in Head and Neck Squamous Cell Carcinoma

et al. 2021

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Introduction: Immune-checkpoint inhibitors have demonstrated a significant survival benefit in metastatic and non-resectable head and neck squamous cell carcinoma (HNSCC). Patients with a combined positivity score (CPS) of 20 and higher benefit the most from therapy. Inaccurate definition of the CPS category might lead to the incorrect stratification of patients to immunotherapy. This study’s main aim was to investigate programmed death-ligand 1 (PD-L1) antigen expression in HNSCC in diverse clinical situations and histological settings. Materials and Methods: This is a prospective cohort study conducted in a tertiary referral medical center. Tissues were investigated for PD-L1 expression using the FDA-approved 22C3 immunohistochemistry assay (Dako). We analyzed potential associations between the CPS category and meaningful demographic, clinical, and outcome metrics. Furthermore, we investigated morphologically separate sites for CPS scores in whole surgical tissue specimens and matched preoperative biopsies. Results: We analyzed 36 patients, of whom 26 had oral cavity SCC and 10 had laryngeal SCC. The overall, disease-specific, and progression-free survival of the HNSCC group of patients were not associated with the CPS category (p = 0.45, p = 0.31, and p = 0.88, respectively). There was a significant (18%, 95% CI 0.65–0.9) inconsistency between the CPS category determined in biopsies versus whole carcinoma analyses. We also found an uneven distribution of whole-tumor CPS attributed to spatial carcinoma invasiveness, tumor differentiation, and inflammatory cell infiltration heterogeneity. Discussion and Conclusions: Our data suggest that careful selection of tumor area for CPS analysis is important. PD-L1 antigen expression, clinically represented by CPS, may be up- or down-categorized in different clinical and pathological circumstances. The high whole-tissue CPS category scatter may clinically result in potential treatment modifications. We argue that CPS analysis requires not only adequacy (at least 100 viable tumor cells), but also correct representation of the tumor microenvironment.

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Section: Discussionsupporting

confidence: 92%

Section: Introductionmentioning

confidence: 98%

Spatial Intratumoral Heterogeneity Expression of PD-L1 Antigen in Head and Neck Squamous Cell Carcinoma

et al. 2021

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“…As IFN‐γ is a potent inducer of PD‐L1 (Lenouvel et al., 2019) this may explain the increase in PD‐L1 in non‐smokers with HNSCC. It is worth noting, PD‐L1 expression is higher in non‐smokers in almost every study of PD‐L1 in OSCC (Ahmadi et al., 2019; Foy et al., 2017; Kogashiwa et al., 2017; Lin et al., 2015; Oliveira‐Costa et al., 2015; de Vicente et al., 2018), while the opposite relation has been seen in other tumours, namely lung SCC (LUSCC). A systemic review has shown higher PD‐L1 levels in current smokers with LUSCC as well as a better response to anti‐PD‐1 treatments (Norum & Nieder, 2018).…”

Section: Discussionmentioning

confidence: 98%

Clinicopathological and prognostic significance of PD‐L1 in oral cancer: A preliminary retrospective immunohistochemistry study

et al. 2020

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Objective To evaluate the relation between PD‐L1 expression in oral cavity squamous cell carcinomas and clinicopathological features as well as survival outcomes. Methods A retrospective immunohistochemical study was carried out on 55 archived tumours from 55 patients. Tumours were stained for PD‐L1 and scored by the proportion of tumour cells with positive membranous staining. PD‐L1 scores were compared to the patient's clinicopathological characteristics for any significant associations. Kaplan–Meier curves were constructed for PD‐L1 positive and negative tumours to investigate any advantage to survival. Results Positive PD‐L1 staining was found in 58% of tumours and was significantly more likely in non‐smokers, non‐drinkers and in tongue squamous cell carcinomas. Increased PD‐L1 was also associated with increased lymphocyte infiltration as well as PD‐L1 staining in lymphocytes and the epithelium adjacent to tumour invasion. No survival benefit was seen from PD‐L1 expression in tumour cells. Conclusions PD‐L1 expression is more common in non‐smokers and non‐drinkers, and its presence in the adjacent non‐tumour epithelium suggests it may be involved in early oncogenesis.

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“…This provides another mechanism by which the adaptive component of the TME can have an estrogen dependent effect on the therapeutic efficacy of ICIs. Several studies examining PD-L1 protein expression in NSCLC showed no difference in PD-L1 expression in men and women (174, 175); however, other cancer types such as oral squamous cell carcinoma has shown more frequent PD-L1 expression in tumors from females than males (176).…”

Section: Immune Checkpoint Modulationmentioning

confidence: 99%

Influence of Estrogen on the NSCLC Microenvironment: A Comprehensive Picture and Clinical Implications

2020

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Lung cancer mortality represents the leading cause of cancer related deaths in the United States and worldwide. Almost half of these deaths occur in female patients, making lung cancer the most common cause of cancer mortality in women with a higher annual mortality rate than breast, uterine, and ovarian cancers combined. The distinct epidemiological, histological and biological presentation of non-small cell lung cancer (NSCLC) in women combined with extensive preclinical data have demonstrated that the female sex hormone β-estradiol (E2) plays an important role in NSCLC tumorigenesis, prognosis, and treatment response. Estrogen receptors are widely expressed on stromal and immune cells, and estrogen-linked signaling pathways are known to be involved in regulating the response of both the innate and adaptive immune system. Immune evasion has been recognized as a "hallmark" of cancer and immunotherapy has re-defined standard of care treatment for NSCLC. Despite these advancements, the low response rates observed in patients treated with immune checkpoint inhibitors has led to a search for mediators of immunosuppression and ways to augment the action of these agents. We focus on emerging data describing sex differences that modulate immunotherapy efficacy in NSCLC, immunosuppressive properties of E2 that lead to a pro-tumor microenvironment (TME), and the translational potential of altering the immune microenvironment by targeting the estrogen signaling pathway. E2-induced modulation affects multiple cell types within the TME, including cancer-associated fibroblasts, tumor infiltrating myeloid cells, and tumor infiltrating lymphocytes, all of which interplay with lung tumor cells via E2 and estrogen receptor engagement, ultimately shaping the TME that may, in part, be responsible for the sex-based disparities observed in NSCLC. An improved understanding of the role of the estrogen pathway in NSCLC anti-cancer immunity may lead to novel therapeutic approaches for altering the TME to improve the efficacy of immunotherapy agents.

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Association of PD-L1 expression in oral squamous cell carcinoma with smoking, sex, and p53 expression

Cited by 22 publications

References 30 publications

Spatial Intratumoral Heterogeneity Expression of PD-L1 Antigen in Head and Neck Squamous Cell Carcinoma

Spatial Intratumoral Heterogeneity Expression of PD-L1 Antigen in Head and Neck Squamous Cell Carcinoma

Clinicopathological and prognostic significance of PD‐L1 in oral cancer: A preliminary retrospective immunohistochemistry study

Influence of Estrogen on the NSCLC Microenvironment: A Comprehensive Picture and Clinical Implications

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