The tumor inflammation signature (TIS) is associated with anti-PD-1 treatment benefit in the CERTIM pan-cancer cohort

Abstract

BackgroundThe 18-gene tumor inflammation signature (TIS) is a clinical research assay that enriches for clinical benefit to immune checkpoint blockade. We evaluated its ability to predict clinical benefit of immunotherapy in cancer patients treated with PD-1 checkpoint inhibitors in routine clinical care.MethodsThe CERTIM cohort is a prospective cohort which includes patients receiving immune checkpoint inhibitors in Cochin University hospital. RNA extracted from 58 archival formalin fixed paraffin embedded tumor blocks (including 38 lung cancers, 5 melanomas, 10 renal carcinomas, 4 urothelial carcinomas and 1 colon carcinoma) was hybridized to a beta version of the NanoString® PanCancer IO360™ CodeSet using nCounter® technology. Gene expression signatures were correlated with tumor responses (by RECIST criteria) and overall survival. PD-L1 immunostaining on tumor cells was assessed in 37 non-small cell lung cancer (NSCLC) samples and tumor mutational burden (TMB) measured by whole exome sequencing in 19 of these.ResultsTIS scores were significantly associated with complete or partial response to anti-PD-1 treatment in the whole cohort (odds ratio = 2.64, 95% CI [1.4; 6.0], p = 0.008), as well as in the NSCLC population (odds ratio = 3.27, 95% CI [1.2; 11.6], p = 0.03). Patients whose tumor had a high TIS score (upper tertile) showed prolonged overall survival compared to patients whose tumor had lower TIS scores, both in the whole cohort (hazard ratio = 0.37, 95% CI [0.18, 0.76], p = 0.005) and in the NSCLC population (hazard ratio = 0.36, 95% CI [0.14, 0.90], p = 0.02). In the latter, the TIS score was independent from either PD-L1 staining on tumor cells (spearman coefficient 0.2) and TMB (spearman coefficient − 0.2).ConclusionsThese results indicate that validated gene expression assay measuring the level of tumor microenvironment inflammation such as TIS, are accurate and independent predictive biomarkers and can be easily implemented in the clinical practice.

The frequency and inter-relationship of PD-L1 expression and tumour mutational burden across multiple types of advanced solid tumours in China

“…A previous study in lung cancer revealed a weak correlation between Tils with PD-L1 expression, but not with TMB [44]. While the sample size in this study was small, our study assessed the correlations of these three biomarkers in a larger size of sample with lung cancer.…”

PD-L1 Is Expressed and Promotes the Expansion of Regulatory T Cells in Acute Myeloid Leukemia

“…Blockade of PD-1 signaling by anti-PD-L1 antibody impaired the interaction between AML cells and Treg cells and improved diseases. It is generally recognized that PD-L1 is extensively detectable on the majority of tumors including solid and hematological malignancies (36,37). In AML, the PD-L1 overexpression usually occurred during therapy, after alloHSCT (38) and therapy with hypomethylating agents (39), such as azaticidine and decitabine, and at the relapse of the disease.…”

Lung metastases share common immune features regardless of primary tumor origin

“…31 Recently, the utility of such signature as an accurate and independent predictive biomarker has been validated in a pan-cancer study analyzing anti-PD-1 treatment benefit in primary tumors. 32 Thus, we propose to treat HIC metastases with immune checkpoint inhibitors, irrespective of their primary site of origin. In agreement, and close to be statistically significant, melanoma metastatic samples classified into HIC and MIC showed better OS than LIC after treatment with anti-PD1 inhibitors pembrolizumab or nivolumab.…”