PD-L1 expression correlates with tumor-infiltrating lymphocytes and better prognosis in patients with HPV-negative head and neck squamous cell carcinomas

Sánchez-Canteli, Mario; Granda-Díaz, Rocío; Rio-Ibisate, Nagore Del; Allonca, Eva; López, Fernando; Agorreta, Jackeline; Garmendia, Irati; Montuenga, Luis M.; García-Pedrero, Juana M.

doi:10.1007/s00262-020-02604-w

Cited by 46 publications

(58 citation statements)

References 33 publications

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“…Sánchez-Canteli et al, 2020 [39] High tumoral infiltration by CD8+ TIL was associated with better survival outcomes.…”

Section: References Key Findingsmentioning

confidence: 99%

“…All the included studies showed a survival advantage for the cases with high CD8+ TIL. The pooled meta-analysis showed an ad- The prognostic value of CD8+ TIL was assessed in six eligible studies for inclusion in the meta-analysis [9,35,[37][38][39]41] (Figure 3). All the included studies showed a survival advantage for the cases with high CD8+ TIL.…”

Section: References Key Findingsmentioning

confidence: 99%

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Tumor-Infiltrating Lymphocytes in the Tumor Microenvironment of Laryngeal Squamous Cell Carcinoma: Systematic Review and Meta-Analysis

et al. 2021

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The presence of tumor-infiltrating lymphocytes (TIL) in the tumor microenvironment has been demonstrated to be of prognostic value in various cancers. In this systematic review and meta-analysis, we investigated the prognostic value of TIL in laryngeal squamous cell carcinoma (LSCC). We performed a systematic search in PubMed for publications that investigated the prognostic value of TIL in LSCC. A meta-analysis was performed including all studies assessing the association between TIL counts in hematoxylin-eosin (HE)-stained sections, for CD8+ and/or CD3+/CD4+ TIL and overall survival (OS) or disease-free survival (DFS). The pooled meta-analysis showed a favorable prognostic role for stromal TIL in HE sections for OS (HR 0.57, 95% CI 0.36–0.91, p = 0.02), and for DFS (HR 0.56, 95% CI 0.34–0.94, p = 0.03). High CD8+ TIL were associated with a prolonged OS (HR 0.62, 95% CI 0.4–0.97, p = 0.04) and DFS (HR 0.73, 95% CI 0.34–0.94, p = 0.002). High CD3+/CD4+ TIL demonstrated improved OS (HR 0.32, 95% CI 0.16–0.9, p = 0.03) and DFS (HR 0.23, 95% CI 0.10–0.53, p = 0.0005). This meta-analysis confirmed the favorable prognostic significance of TIL in LSCC. High stromal TIL evaluated in HE sections and intra-tumoral and stromal CD3+, CD4+ and/or CD8+ TIL might predict a better clinical outcome.

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“…Sánchez-Canteli et al, 2020 [39] High tumoral infiltration by CD8+ TIL was associated with better survival outcomes.…”

Section: References Key Findingsmentioning

confidence: 99%

Section: References Key Findingsmentioning

confidence: 99%

Tumor-Infiltrating Lymphocytes in the Tumor Microenvironment of Laryngeal Squamous Cell Carcinoma: Systematic Review and Meta-Analysis

et al. 2021

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“…The infiltration of lymphocytes has been reported to imply an adaptive immunity against tumor progression and positively impact clinical survival in a variety of tumor types including gliomas (Lohr et al, 2011;Sanchez-Canteli et al, 2020). However, conflicting evidences exist.…”

Section: Discussionmentioning

confidence: 99%

CARD-Associated Risk Score Features the Immune Landscape and Predicts the Responsiveness to Anti-PD-1 Therapy in IDH Wild-Type Gliomas

Lin

et al. 2021

Front. Cell Dev. Biol.

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BackgroundProteins containing the caspase recruitment domain (CARD) play critical roles in cell apoptosis and immunity. However, the impact of CARD genes in tumor immune cell infiltration, responsiveness to checkpoint immunotherapy, and clinical outcomes of gliomas remains unclear. Here, we explore using CARD genes to depict the immune microenvironment and predict the responsiveness of gliomas to anti-PD-1 therapy.MethodsThe genome and transcriptome data of 231 patients with isocitrate dehydrogenase wild-type (IDH-wt) gliomas were retrieved from The Cancer Genome Atlas (TCGA) database to screen CARD genes associated with T lymphocyte infiltration in gliomas. Weighted co-expression network and LASSO penalized regression were employed to generate a CARD-associated risk score (CARS). Two independent and publicly available datasets were used to validate the effectiveness of CARS.ResultsThe CARS divided the 231 glioma patients into high- and low-risk subgroups with distinct immune microenvironment and molecular features. The high-risk group had high CARS and was characterized by enrichment of dysfunctional T lymphocytes in a profound immunosuppressive microenvironment, whereas the low-risk group had low CARS and exhibited an immune exclusion genotype. Moreover, signaling aberrations including upregulation of PI3K/Akt/mTOR, NF-κB, and TGF-β were found in the high-risk group. In contrast, the activated WNT pathway was more evident in the low-risk group. Furthermore, we found that an elevated CARS indicated a decreased overall survival for IDH-wt gliomas under standard care but a clinical benefit from checkpoint immunotherapy.ConclusionThis study developed an immune- and prognosis-relevant risk score, which could be used to enhance our understanding of the heterogeneity of immune microenvironment of gliomas and facilitate to identify patients who will benefit from checkpoint immunotherapy.

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“…Moreover, recent studies have demonstrated that the spatial distribution patterns of TILs within the tumor microenvironment may play an even more drastic role in determining the prognostic outcome, than the density of TILs alone (20)(21)(22). In yet other studies, the co-assessment of immune cell signatures related to specific functional status (or subtypes) of TILs may be critical for a more accurate assessment of prognostic outcomes (23)(24)(25)(26)(27)(28)(29)(30). These observations collectively suggest that T cell trafficking into the TME is one of the critical aspects of antitumor immunity.…”

Section: Introductionmentioning

confidence: 99%

The Cancer Cell Dissemination Machinery as an Immunosuppressive Niche: A New Obstacle Towards the Era of Cancer Immunotherapy

et al. 2021

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Although cancer immunotherapy has resulted in unpreceded survival benefits to subsets of oncology patients, accumulating evidence from preclinical animal models suggests that the immunosuppressive tumor microenvironment remains a detrimental factor limiting benefit for many patient subgroups. Recent efforts on lymphocyte-mediated immunotherapies are primarily focused on eliminating cancer foci at primary and metastatic sites, but few studies have investigated the impact of these therapies on the highly complex process of cancer cell dissemination. The metastatic cascade involves the directional streaming of invasive/migratory tumor cells toward specialized blood vessel intravasation gateways, called TMEM doorways, to the peripheral circulation. Importantly, this process occurs under the auspices of a specialized tumor microenvironment, herewith referred to as “Dissemination Trajectory”, which is supported by an ample array of tumor-associated macrophages (TAMs), skewed towards an M2-like polarization spectrum, and which is also vital for providing microenvironmental cues for cancer cell invasion, migration and stemness. Based on pre-existing evidence from preclinical animal models, this article outlines the hypothesis that dissemination trajectories do not only support the metastatic cascade, but also embody immunosuppressive niches, capable of providing transient and localized immunosubversion cues to the migratory/invasive cancer cell subpopulation while in the act of departing from a primary tumor. So long as these dissemination trajectories function as “immune deserts”, the migratory tumor cell subpopulation remains efficient in evading immunological destruction and seeding metastatic sites, despite administration of cancer immunotherapy and/or other cytotoxic treatments. A deeper understanding of the molecular and cellular composition, as well as the signaling circuitries governing the function of these dissemination trajectories will further our overall understanding on TAM-mediated immunosuppression and will be paramount for the development of new therapeutic strategies for the advancement of optimal cancer chemotherapies, immunotherapies, and targeted therapies.

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PD-L1 expression correlates with tumor-infiltrating lymphocytes and better prognosis in patients with HPV-negative head and neck squamous cell carcinomas

Cited by 46 publications

References 33 publications

Tumor-Infiltrating Lymphocytes in the Tumor Microenvironment of Laryngeal Squamous Cell Carcinoma: Systematic Review and Meta-Analysis

Tumor-Infiltrating Lymphocytes in the Tumor Microenvironment of Laryngeal Squamous Cell Carcinoma: Systematic Review and Meta-Analysis

CARD-Associated Risk Score Features the Immune Landscape and Predicts the Responsiveness to Anti-PD-1 Therapy in IDH Wild-Type Gliomas

The Cancer Cell Dissemination Machinery as an Immunosuppressive Niche: A New Obstacle Towards the Era of Cancer Immunotherapy

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