Pembrolizumab in Recurrent Squamous Cell Carcinoma of the Vulva: Case Report and Review of the Literature

Shields, Lisa B. E.; Gordinier, Mary E.

doi:10.1159/000491090

Cited by 32 publications

(25 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Little is known about the PD-L1 status in SCCV, but high frequency of PD-L1 expression was also reported by a few other studies (Choschzick et al 2018;Hecking et al 2017;Thangarajah et al 2019). Currently clinical data about checkpoint-inhibitor therapy in SCCV are limited, although responsiveness was reported for single cases (Shields and Gordinier 2019;Ott et al 2019). With regard to locally advanced, recurrent or metastatic courses of disease, a Many studies aimed to determine the prognostic impact of PD-L1 expression on the patient's survival.…”

Section: Discussionmentioning

confidence: 99%

“…Immunostaining for PD-L1 has become a valid predictive biomarker that is routinely analyzed in several types of cancer. So far single case reports could demonstrate that PD-L1 inhibitors might be useful in SCCV (Shields and Gordinier 2019;Ott et al 2019). Regarding different tumor types studies are controversial, whether PD-L1 expression is a prognostic marker too (Troiano et al 2019;Wang et al 2017;Wang 2019).…”

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

See 1 more Smart Citation

PD-L1 expression and survival in p16-negative and -positive squamous cell carcinomas of the vulva

Czogalla

Pham

Trillsch

et al. 2020

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

Aim Programmed death-ligand 1 (PD-L1) has become a widely used predictive biomarker for therapy with checkpoint inhibitors in a variety of cancers. Here, we studied the expression of PD-L1 in squamous cell carcinomas of the vulva (SCCV) with regard to HPV status via its surrogate marker p16. Additionally, the status of PD-L1 and p16 were analyzed for prognostic information and potential correlation to tumor-infiltrating lymphocytes (TILs). Methods PD-L1 was analyzed in 128 cases of SCCV using the tumor proportion score (TPS), the immune cell score (ICS) and the combined positive score (CPS). Cases were immunostained for p16 and analyzed for stromal TILs. PD-L1, p16, and TILs were compared to clinico-pathological parameters and patient's survival. Results TPS ≥ 50% and CPS ≥ 50 were correlated to a worse grading (p = 0.028 and p = 0.031), but not to FIGO-stage. CPS ≥ 50 was associated to a worse prognosis with overall survival (p = 0.021) but was not correlated to the progression-free survival. P16-positivity was correlated to a longer progression-free survival (p = 0.006) and overall survival (p = 0.023). PD-L1 expression was independent from p16 status. TILs ≥ 50% were present in 24% of the cases and were strongly correlated to PD-L1 (TPS p = 0.02, ICS p < 0.001, CPS p = 0.001). Conclusion Our data demonstrate that PD-L1 expression is frequent in SCCV and independent from p16 status. High PD-L1 expression was associated with an unfavorable outcome whereas p16-positivity turned out to be an independent positive prognostic factor.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Electronic Supplementary Materialsmentioning

confidence: 99%

PD-L1 expression and survival in p16-negative and -positive squamous cell carcinomas of the vulva

Czogalla

Pham

Trillsch

et al. 2020

J Cancer Res Clin Oncol

View full text Add to dashboard Cite

show abstract

“…Altogether, this makes a strong case for the treatment of inflamed and immune altered-excluded VSCC with PD-1/PD-L1 checkpoint therapy. Indeed, a first successfully treated case with advanced stage recurrent vulvar cancer has been reported with PD-L1 blockade [39]. A tumor-specific increase of the CD4+ T-cell response seems more likely to be achieved by CTLA4-blockade than by targeting PD-1 [40], arguing for a combination of PD-L1 and CTLA-4 blockade to reinvigorate the tumor-specific CD4+ T-cell response.…”

Section: Discussionmentioning

confidence: 99%

High numbers of activated helper T cells are associated with better clinical outcome in early stage vulvar cancer, irrespective of HPV or p53 status

Kortekaas¹,

Santegoets²,

Abdulrahman³

et al. 2019

j. immunotherapy cancer

View full text Add to dashboard Cite

Background Vulvar squamous cell carcinoma (VSCC) has been suggested to consist of three subtypes; HPV-positive, HPV-negative mutated TP53 or HPV-negative TP53 wildtype, with different clinical courses. To analyze the immune infiltrate in these molecular subtypes and its impact on clinical outcome, an in-depth study of the tumor immune microenvironment was performed. Methods Sixty-five patients with invasive VSCC matched for age, FIGO stage and treatment modality, were grouped according to the presence of HPV and p53 protein expression status. Archived tissues were analyzed for intraepithelial and stromal expression of CD3, CD8, Foxp3, PD-1, and pan-keratin in randomly selected areas using immunofluorescence. Additional phenotyping of T cells was performed ex-vivo on VSCC ( n = 14) and blood samples by flow cytometry. Healthy vulvar samples and blood served as controls. Results Based on T-cell infiltration patterns about half of the VSCC were classified as inflamed or altered-excluded while one-third was immune-deserted. High intraepithelial helper T cell infiltration was observed in 78% of the HPV-induced VSCC, 60% of the HPVnegVSCC/p53wildtype and 40% of the HPVnegVSCC with abnormal p53 expression. A high intraepithelial infiltration with activated (CD3 + PD-1 + ), specifically helper T cells (CD3 + CD8 − Foxp3 − ), was associated with a longer recurrence-free period and overall survival, irrespective of HPV and p53 status. Flow cytometry confirmed the tumor-specific presence of activated (CD4 + PD-1 ++ CD161 − CD38 + HLA-DR + and CD8 + CD103 + CD161 − NKG2A +/− PD1 ++ CD38 ++ HLA-DR + ) effector memory T cells. Conclusion This is the first study demonstrating an association between intraepithelial T cells and clinical outcome in VSCC. Our data suggest that abnormal p53 expressing VSCCs mostly are cold tumors whereas HPV-driven VSCCs are strongly T-cell infiltrated. Electronic supplementary material The online version of this article (10.1186/s40425-019-0712-z) contains supplementary material, which is available to authorized users.

show abstract

“…Vulvar cancer is one of the less frequently diagnosed gynecological cancers, with 6120 new cases predicted to be encountered in the US in 2020 and 1350 deaths expected due to this disease (Table 1) [1]. PD-L1 is reported to be expressed in most vulva squamous cell carcinoma [6,142,143], even though the significance of this parameter is not yet well understood. Clinical trials for vulvar and vaginal cancer are often part of basket studies of HPV-associated cancers (CheckMate 358).…”

Section: Cervical and Other Female Gynecologic Cancersmentioning

confidence: 99%

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

Drakes

Czerlanis

Stiff

2020

Cancers

View full text Add to dashboard Cite

This review provides an update on the current use of immune checkpoint inhibitors (ICI) in female gynecologic cancers, and it addresses the potential of these agents to provide therapy options for disease management and long-term remission in advanced disease patients, where surgery, chemotherapy, and/or radiation fail to meet this goal. The topic of immune checkpoint inhibitors (ICI) blocking cytotoxic T lymphocyte associated protein-4 (CTLA-4) and the programmed death-1 (PD-1) axis has come to the forefront of translational medicine over the last decade for several malignancies. The text will focus primarily on a discussion of ovarian cancer, which is the most frequent cause of death of gynecologic cancers; endometrial cancer, which is the most often diagnosed gynecologic cancer; and cervical cancer, which is the third most common female gynecologic malignancy, all of which unfavorably alter the lives of many women. We will address the critical factors that regulate the outcome of these cancer types to ICI therapy, the ongoing clinical trials in this area, as well as the adverse immune responses that impact the outcome of patients given ICI regimens.

show abstract

Pembrolizumab in Recurrent Squamous Cell Carcinoma of the Vulva: Case Report and Review of the Literature

Cited by 32 publications

References 30 publications

PD-L1 expression and survival in p16-negative and -positive squamous cell carcinomas of the vulva

PD-L1 expression and survival in p16-negative and -positive squamous cell carcinomas of the vulva

High numbers of activated helper T cells are associated with better clinical outcome in early stage vulvar cancer, irrespective of HPV or p53 status

Immune Checkpoint Blockade in Gynecologic Cancers: State of Affairs

Contact Info

Product

Resources

About