Screening a Broad Range of Solid and Haematological Tumour Types for CD70 Expression Using a Uniform IHC Methodology as Potential Patient Stratification Method.

Tal Flieswasser,Alina Danu,Hans De Haard,Piotr Zabrocki,Valérie Camara-Clayette,Julie Jacobs,Evelien Smits,Patrick Pauwels,Vincent Ribrag,Luc Van Rompaey,Karen Zwaenepoel,Jacques Bosq

doi:10.3390/cancers11101611

Abstract

The constitutive expression of CD70 has been described in various haematological and solid tumour types. In addition, the co-expression of its receptor in tumours has been demonstrated, mediating tumour cell proliferation. Although CD70 expression is a prerequisite to enrol patients in solid tumour clinical trials using anti-CD70 immunotherapy, there is currently no standardised test to evaluate CD70 expression. These differences in immunohistochemistry (IHC) protocols make it challenging to compare the expression levels that were obtained in different studies, pointing out the need for one uniform methodology. In this retrospective study, over 600 tumour samples from different solid and haematological malignancies were analysed while using one validated IHC method. CD70 and CD27 expression was demonstrated in a broad range of tumour types. In solid tumours, 43% demonstrated CD70 positivity with the highest degree in renal cell carcinoma (79.5%). Kaposi sarcoma showed no CD70 expression on the tumour cells. In lymphoma samples, 58% demonstrated CD70 positivity. Moreover, the co-expression of CD70 and CD27 was observed in 39% of lymphoma samples. These findings highlight the need to further explore anti-CD70 therapies in a broad range of CD70 expressing tumour types and in doing so, implementing one standardised protocol to define CD70 overexpression to use it as a diagnostic tool.

Highlights

Numerous successful clinical trials have led to a great number of FDA approvals for PD-1/PD-L1 blockade therapy in a spectrum of different tumour types: melanoma, non-small cell lung cancer, urothelial carcinoma, classic Hodgkin lymphoma, renal cell carcinoma, Merkel cell carcinoma, hepatocellular carcinoma, gastric carcinomas, and head and neck squamous cell carcinoma
Anti-CD70 immunotherapy is being evaluated in clinical trials and it has been associated with objective clinical responses against various CD70 positive malignancies [17]
CD70 expression was assessed in 25 different solid tumour types (N = 496), which ranged from two to 101 samples per tumour type (Figure 1)

Summary

Introduction

Numerous successful clinical trials have led to a great number of FDA approvals for PD-1/PD-L1 blockade therapy in a spectrum of different tumour types: melanoma, non-small cell lung cancer, urothelial carcinoma, classic Hodgkin lymphoma, renal cell carcinoma, Merkel cell carcinoma, hepatocellular carcinoma, gastric carcinomas, and head and neck squamous cell carcinoma. Show clinical response to monotherapy, pointing out the possibility that alternative pathways may have significant impact on the antitumor immune activity in patients with various tumour types [1,2]. In this regard, CD70 is a ligand of the tumour necrosis factor superfamily, of which its expression is tightly regulated under physiological conditions: it is only transiently expressed on antigen-activated. Thereof, 92% response rates could be seen in acute myeloid leukaemia patients while using CD70-targeting antibodies in a Phase 1 trial [18]

Methods

Results

Conclusion