In the Journals

PD-L1 expression may predict immunotherapy response in cervical, vulvar squamous cell carcinoma

Recurrent copy number gains to the genes that encode the PD-1 ligands appeared associated with PD-L1 expression in certain patients with cervical and vulvar squamous cell carcinoma, according to a genetic analysis.

These genetic expressions could help identify patients who may benefit from therapies targeting programmed cell death protein 1 (PD-1), according to the researchers.

Patients with squamous cell carcinomas of the cervix and vulva have limited therapeutic options, and advances in immunotherapy may be beneficial for this population, according to study background.

“Tumors employ strategies of immune evasion to survive and spread,” Scott J. Rodig, MD, PhD, associate professor of pathology at Harvard Medical School and Brigham and Women’s Hospital, and colleagues wrote. “A major mechanism involves expression of programmed cell death 1 ligands 1 and 2 (PD-L1, PD-L2) by tumor cells that bind PD-1 ... on effector T cells to suppress antitumor cellular immunity. Clinical responses to PD-1 blockade are associated with PD-L1 expression by malignant tumor cells and provide a rationale for screening individual tumors to identify patients most likely to benefit.”

Rodig and colleagues decided to determine the genetic status of CD274, which encodes PD-L1, and PDCD1LG2, which encodes PD-L2, in women with cervical or vulvar squamous cell carcinoma. They further sought to correlate their findings with PD-L1 protein expression.

The researchers performed fluorescence in situ hybridization (FISH) on 71 formalin-fixed, paraffin-embedded biopsy samples (cervical squamous cell carcinoma, n = 48; vulvar squamous cell carcinoma, n = 23), using probes targeting CD274, PDCD1LG2 and the centromeric portion of chromosome 9.

They further performed immunohistochemistry, using an antibody that recognized PD-L1.

The researchers categorized the tumors according to genetic abnormalities as identified by FISH (coamplification, cogain, polysomy and disomy).

Sixty-seven percent (n = 32) of cervical squamous cell carcinomas and 43% (n = 10) of vulvar squamous cell carcinomas had coamplifications or cogains in CD274 or PDCD1LG2. Nine cervical tumors (19%) and six vulvar tumors (26%) were polysomic. Seven cervical tumors (15%) and seven vulvar tumors (30%) were disomic.

The highest median PD-L1 protein expression occurred in tumors with CD274 or PDCD1LG2 coamplification. Disomic tumors had the lowest PD-L1 expression.

“A recent trial of single-agent nivolumab [Opdivo, Bristol-Myers Squibb] in patients with relapsed and/or refractory classical Hodgkin’s lymphoma revealed the highest overall response rate (87%) reported to date for an individual tumor type,” Rodig and colleagues wrote. “Tissue biopsies were available for a subset of patients in this trial, and all showed copy gain of CD274 and PDCD1LG2. ... Thus, a significant proportion of patients with [cervical and vulvar squamous cell carcinoma] tumors are rational candidates for clinical trials of PD-1 blockade.” – by Cameron Kelsall

Disclosure: Rodig and two other study researchers report research funding from the International Immune Oncology Network, which is owned by Bristol-Myers Squibb. One study researcher reports owning a patent related to PD-1 ligand diagnostics. The other researchers report no relevant financial disclosures.

Recurrent copy number gains to the genes that encode the PD-1 ligands appeared associated with PD-L1 expression in certain patients with cervical and vulvar squamous cell carcinoma, according to a genetic analysis.

These genetic expressions could help identify patients who may benefit from therapies targeting programmed cell death protein 1 (PD-1), according to the researchers.

Patients with squamous cell carcinomas of the cervix and vulva have limited therapeutic options, and advances in immunotherapy may be beneficial for this population, according to study background.

“Tumors employ strategies of immune evasion to survive and spread,” Scott J. Rodig, MD, PhD, associate professor of pathology at Harvard Medical School and Brigham and Women’s Hospital, and colleagues wrote. “A major mechanism involves expression of programmed cell death 1 ligands 1 and 2 (PD-L1, PD-L2) by tumor cells that bind PD-1 ... on effector T cells to suppress antitumor cellular immunity. Clinical responses to PD-1 blockade are associated with PD-L1 expression by malignant tumor cells and provide a rationale for screening individual tumors to identify patients most likely to benefit.”

Rodig and colleagues decided to determine the genetic status of CD274, which encodes PD-L1, and PDCD1LG2, which encodes PD-L2, in women with cervical or vulvar squamous cell carcinoma. They further sought to correlate their findings with PD-L1 protein expression.

The researchers performed fluorescence in situ hybridization (FISH) on 71 formalin-fixed, paraffin-embedded biopsy samples (cervical squamous cell carcinoma, n = 48; vulvar squamous cell carcinoma, n = 23), using probes targeting CD274, PDCD1LG2 and the centromeric portion of chromosome 9.

They further performed immunohistochemistry, using an antibody that recognized PD-L1.

The researchers categorized the tumors according to genetic abnormalities as identified by FISH (coamplification, cogain, polysomy and disomy).

Sixty-seven percent (n = 32) of cervical squamous cell carcinomas and 43% (n = 10) of vulvar squamous cell carcinomas had coamplifications or cogains in CD274 or PDCD1LG2. Nine cervical tumors (19%) and six vulvar tumors (26%) were polysomic. Seven cervical tumors (15%) and seven vulvar tumors (30%) were disomic.

The highest median PD-L1 protein expression occurred in tumors with CD274 or PDCD1LG2 coamplification. Disomic tumors had the lowest PD-L1 expression.

“A recent trial of single-agent nivolumab [Opdivo, Bristol-Myers Squibb] in patients with relapsed and/or refractory classical Hodgkin’s lymphoma revealed the highest overall response rate (87%) reported to date for an individual tumor type,” Rodig and colleagues wrote. “Tissue biopsies were available for a subset of patients in this trial, and all showed copy gain of CD274 and PDCD1LG2. ... Thus, a significant proportion of patients with [cervical and vulvar squamous cell carcinoma] tumors are rational candidates for clinical trials of PD-1 blockade.” – by Cameron Kelsall

Disclosure: Rodig and two other study researchers report research funding from the International Immune Oncology Network, which is owned by Bristol-Myers Squibb. One study researcher reports owning a patent related to PD-1 ligand diagnostics. The other researchers report no relevant financial disclosures.