Physical Poster + E-Poster Presentation 34th Lorne Cancer Conference 2022

Multispectral immunohistochemical immune profiling of patients with rare gynaecological malignancies and high mutational burden (#223)

Luke T Quigley 1 , Oliver Klein 1 2 , Damien Kee 2 3 , Bo Goa 4 , Ben Markman 5 6 , Jessica Da Gama Da Gama Duarte 1 , Louise Jackett 7 , Linda Mileshkin 3 , Richelle Linklater 3 , Andrew Strickland 5 6 , Jodie Palmer 2 , Clare Scott 3 , Matteo Carlino 4 , Andreas Behren 1 8 , Jonathan Cebon 1 2 8
  1. Olivia Newton-John Cancer Research Institute, and School of Cancer Medicine, La Trobe University, Heidelberg, Victoria, Australia, Heidelberg, Victoria, Australia
  2. Department of Medical Oncology, Olivia Newton-John Cancer Centre, Austin Health, Melbourne, Australia, Melbourne, Victoria, Australia
  3. Department of Medical Oncology, Peter McCallum Cancer Centre, Melbourne, Australia, Melbourne, Victoria
  4. Blacktown Hospital and the University of Sydney, Sydney, Australia, Sydney, Victoria
  5. Department of Medical Oncology, Monash Health, Melbourne, Australia, Melbourne, Victoria
  6. Monash University, Melbourne, Australia, Melbourne, Victoria
  7. Department of Anatomical Pathology, Austin Health, Melbourne, Australia, Melbourne, Victoria
  8. Department of Medicine, University of Melbourne, Melbourne, Australia, Melbourne, Victoria

 

Patients burdened with rare cancers represent 55% of all gynaecological malignancies and have inferior survival outcomes compared to patients with more common cancers. A multicentre phase 2 study (CA209-538) demonstrated significant clinical efficacy in treating a range of advanced rare gynaecological malignancies with combination immunotherapy containing anti-PD-1 antibody (nivolumab) and anti-CTLA-4 antibody (ipilimumab). Although patients with hypermutated tumours are often responsive to immunotherapy, this was not seen for two patients (tumour mutation burden: 1535/MB and 1022/MB) within the trial, warranting further investigation.

Archival formalin-fixed paraffin-embedded tumour tissue from these two patients were investigated for expression of CD3, CD4, CD8, CD19, CD68, Granzyme B, FOXP3, MHC Class 1, PD-L1, and PanCK using multiplex immunohistochemistry.

The hypermutated uterine serous carcinoma was found to be heavily infiltrated by CD3+ T cells and CD4+FOXP3+ regulatory T cells, while the hypermutated ovarian carcinosarcoma demonstrated low-level T cell infiltration with an increased frequency of CD68+ macrophages. Both hypermutated tumours exhibited concomitant loss of MHC-I class expression on tumour cells, which in combination with increased numbers of regulatory T cells and/or lack of low-level T cell infiltration are likely indicators of tumour immune evasion and regulation.

Investigation of immune cell infiltration and MHC-I class expression in pre-treatment tumour tissues may aid in predicting response to combination immunotherapy.