Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade

Lipson, Evan J.; Lilo, Mohammed; Ogurtsova, Aleksandra; Esandrio, Jessica; Xu, Huimin; Schollenberger, Megan D.; Sharfman, William H.; Taube, Janis M.

doi:10.1186/s40425-017-0228-3

Cited by 129 publications

(119 citation statements)

References 30 publications

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“…Staining for PD-L1 (15) and PD-1 (16) was performed as previously described. Immunohistochemistry (IHC) staining for LAG3, CD8, and CD163 were performed according to standardized institutional protocols.…”

Section: Methodsmentioning

confidence: 99%

Characterization of the Immune Microenvironment in Hepatocellular Carcinoma

Yarchoan

Xing

Luan

et al. 2017

Clinical Cancer Research

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124

102

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Purpose Hepatocellular carcinoma (HCC) often arises in the setting of chronic liver inflammation and may be responsive to novel immunotherapies. Experimental Design To characterize the immune microenvironment in HCC, IHC staining was performed for CD8-positive T lymphocytes, PD-1–positive, and LAG-3–positive lymphocytes, CD163-positive macrophages, and PD-L1 expression in tumor and liver background from 29 cases of resected HCC. Results Expression of CD8 was reduced in tumor, and expression of CD163 was reduced at the tumor interface. Positive clusters of PD-L1 expression were identified in 24 of 29 cases (83%), and positive expression of LAG-3 on tumor-infiltrating lymphocytes was identified in 19 of 29 cases (65%). The expression of both PD-L1 and LAG-3 was increased in tumor relative to liver background. No association between viral status or other clinicopathologic features and expression of any of the IHC markers investigated was noted. Conclusions LAG-3 and PD-L1, two inhibitory molecules implicated in CD8 T-cell tolerance, are increased in most HCC tumors, providing a basis for investigating combinatorial checkpoint blockade with a LAG-3 and PD-L1 inhibitor in HCC.

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Section: Methodsmentioning

confidence: 99%

Characterization of the Immune Microenvironment in Hepatocellular Carcinoma

Yarchoan

Xing

Luan

et al. 2017

Clinical Cancer Research

Self Cite

124

102

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“…Significant expression of PD-L1 on tumor and tumor-infiltrating immune cells was observed. In another series of 40 basal cell carcinoma specimens, PD-L1 expression on tumor cells was observed in 22% of the cases, and in 82%, PD-L1 positivity was documented on tumor-infiltrating immune cells [18]. 1 patient of this series with PD-L1 positivity showed objective tumor response to pembrolizumab.…”

Section: Discussionmentioning

confidence: 99%

Anti-PD-1 Therapy Leads to Near-Complete Remission in a Patient with Metastatic Basal Cell Carcinoma

et al. 2018

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Background: Metastatic basal cell carcinoma is rare and the prognosis is poor, with a lack of established treatment options for patients progressing on or after treatment with inhibitors of the hedgehog signaling pathway. Case Report: A man with pulmonary metastases of a basal cell carcinoma progressing after treatment with sonidegib and vismodegib was started on treatment with the anti-PD-1 antibody pembrolizumab. Upon treatment, rapid clinical improvement occurred, and after 5 cycles, the computed tomography scan showed near-complete remission of all tumor lesions. The tumor cells showed the absence of PD-L1 expression. Discussion: We report the first case of a patient with metastatic basal cell carcinoma experiencing an exceptional response to treatment with pembrolizumab in the absence of PD-L1 expression on the tumor cells. Immune checkpoint inhibition seems a promising treatment strategy for metastatic basal cell carcinoma. Our case suggests that the lack of PD-L1 expression does not rule out potential benefit from checkpoint inhibitor treatment.

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“…79 Early reports suggest that patients with aggressive squamous cell and basal cell carcinomas may also respond to immune checkpoint blockade therapy. 80–82 …”

Section: Melanoma and Other Cutaneous Malignanciesmentioning

confidence: 99%

Implications of the tumor immune microenvironment for staging and therapeutics

et al. 2018

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Characterizing the tumor immune microenvironment enables the identification of new prognostic and predictive biomarkers, the development of novel therapeutic targets and strategies, and the possibility to guide first-line treatment algorithms. Although the driving elements within the tumor microenvironment of individual primary organ sites differ, many of the salient features remain the same. The presence of a robust antitumor milieu characterized by an abundance of CD8+ cytotoxic T-cells, Th1 helper cells, and associated cytokines often indicates a degree of tumor containment by the immune system and can even lead to tumor elimination. Some of these features have been combined into an ‘Immunoscore’, which has been shown to complement the prognostic ability of the current TNM staging for early stage colorectal carcinomas. Features of the immune microenvironment are also potential therapeutic targets, and immune checkpoint inhibitors targeting the PD-1/ PD-L1 axis are especially promising. FDA-approved indications for anti-PD-1/PD-L1 are rapidly expanding across numerous tumor types and, in certain cases, are accompanied by companion or complimentary PD-L1 immunohistochemical diagnostics. Pathologists have direct visual access to tumor tissue and in-depth knowledge of the histological variations between and within tumor types and thus are poised to drive forward our understanding of the tumor microenvironment. This review summarizes the key components of the tumor microenvironment, presents an overview of and the challenges with PD-L1 antibodies and assays, and addresses newer candidate biomarkers, such as CD8+ cell density and mutational load. Characteristics of the local immune contexture and current pathology-related practices for specific tumor types are also addressed. In the future, characterization of the host antitumor immune response using multiplexed and multimodality biomarkers may help predict which patients will respond to immune-based therapies.

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Basal cell carcinoma: PD-L1/PD-1 checkpoint expression and tumor regression after PD-1 blockade

Cited by 129 publications

References 30 publications

Characterization of the Immune Microenvironment in Hepatocellular Carcinoma

Characterization of the Immune Microenvironment in Hepatocellular Carcinoma

Anti-PD-1 Therapy Leads to Near-Complete Remission in a Patient with Metastatic Basal Cell Carcinoma

Implications of the tumor immune microenvironment for staging and therapeutics

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