An Immunoscore for Ovarian Cancer: Preliminary Evidence for Predicting the Ability to Expand Tumour-Infiltrating Lymphocytes from Surgical Biopsies


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James Platt1,Gemma Owens1,Richard Edmondson2
1The University of Manchester,2The University of MAnchester

Abstract

Background

Adoptive cell therapy using tumour-infiltrating lymphocytes (TILs) is an exciting therapeutic prospect in ovarian cancer. TIL therapy relies upon the ex vivo expansion of autologous TILs, which is highly variable and unpredictable. We have adapted the colorectal cancer 'immunoscore' to predict TIL expansion from ovarian cancer biopsies and guide the stratification of patients to TIL therapy, and other immunotherapies, effectively. 

Method

Immunohistochemical staining for T cell markers CD3, CD8 and CD45RO, and the development of a tailored scoring system, allowed quantification of the immune infiltrate in ovarian and omental tumour biopsies. A multiplex immunofluorescence protocol was also developed. TILs were isolated from corresponding biopsies and expanded, with final yields subsequently correlated with the immunoscore. Chemotherapy-sensitivity and progression-free survival (PFS) were also determined and correlated with the immunoscore.

Results

Surgical biopsies were collected from 29 ovarian cancer patients. The immunoscore was predictive of TIL expansion; however, this lacked significance (AUC=0.6625; P=0.12). Predictive value improved for CD8 count alone (AUC=0.6917; P=0.07). A marked trend was observed for greater TIL expansion from tumours with high immunoscores, compared to low immunoscores (P=0.0778). Trends also existed for greater chemotherapy-sensitivity and PFS with higher omental immunoscores, compared to lower immunoscores (P=0.12 and P=0.1, respectively).

Conclusion

There is great potential for predicting TIL expansion using the immunoscore. The predictive value may improve by incorporating an immunosuppressive marker, such as FOXP3. Furthermore, overcoming limitations relating to the subjectivity of immunohistochemistry and the molecular heterogeneity of ovarian cancer would enhance clinical utility. This study provides, for the first time, evidence for predicting TIL expansion from ovarian cancer biopsies using the immunoscore. This relationship requires validation in a second, larger patient cohort.