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P182 The immune landscape is a strong predictive biomarker for clinical outcome in early stage vulvar cancer, irrespective of HPV or p53 status
  1. KE Kortekaas1,2,
  2. SJAM Santegoets2,
  3. Z Abdulrahman2,
  4. VJ van Ham2,
  5. M van der Tol1,
  6. I Ehsan3,
  7. HC van Doorn4,
  8. T Bosse5,
  9. MIE van Poelgeest1 and
  10. SH van der Burg2
  1. 1Gynecology
  2. 2Medical Oncology, Oncode Institute, Leiden University Medical Center
  3. 3Medical Oncology, Oncode Institute, Leiden University Medical Centre, Leiden
  4. 4Gynecology, Erasmus MC Cancer Institute, Rotterdam
  5. 5Pathology, Leiden University Medical Center, Leiden, The Netherlands


Introduction/Background Vulvar squamous cell carcinoma (VSCC) consists of three subtypes; HPV-related, HPV-negative TP53 wildtype and HPV-negative mutated TP53 (HPVposVSCC, HPVnegVSCC/p53wt, and HPVnegVSCC/p53abn, respectively) which are all treated by mutilating radical surgery and/or (chemo)radiotherapy. Despite the fact that the immune system plays a key role in cancer, the knowledge on its effect in VSCC is limited at best. A study, elucidating the clinical impact of tumor-immunity in VSCC was, therefore, performed with the aim to foster the development of immunotherapeutic approaches.

Methodology Sixty-five patients with early-stage VSCC were categorized based on HPV and p53 status. Archived tissues were analyzed for 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 and blood samples by flow cytometry. Healthy vulvar tissue and blood served as controls.

Results T-cell infiltration of VSCC was highly variable between patients, ranging from completely absent to very high numbers, and differed per VSCC subtype. Approximately 80% of the HPVposVSCC showed high T-cell infiltration, followed by 60% of the HPVnegVSCC/p53wt, and 40% of the HPVnegVSCC/p53abn. Importantly, high T-cell infiltration was associated with longer recurrence-free period and overall survival, irrespective of the HPV and p53 status. In-depth analysis of tumor-infiltrating T cells with flow cytometry confirmed the tumor-specific presence of activated effector memory T cells in VSCC and revealed that most of the CD4+ and CD8+ T cells expressed PD-1.

Conclusion This study is the first to show a strong correlation between T-cell infiltration and clinical outcome. Our data suggest the application of two immunotherapeutic strategies depending on immune phenotype. The high expression of PD-1 in T-cell infiltrated tumors alludes to anti-PD1 blockade, whereas VSCC tumors with low numbers of intratumoral T cells should be stimulated with inflammatory reagents to stimulate local immune responses.

Disclosure Nothing to disclose.

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