Correlation between PD-1 and PD-L1 expression profile, NLR, LDH and Objective Response Rate, PFS and OS in advanced NSCLC after immunotherapy

In recent years, immunotherapy has revolutionized and changed the standard of care in patients with advanced non-small cell lung cancer (NSCLC).
And the assessment of PDL1 expression profile has acquired a significant role in the treatment decisional path not only in patients with advanced NSCLC but also for different solid tumours.
For each PD-1/PDL1 inhibitor, a specific PD-L1 immunohistochemistry (IHC) assay was developed to assess PD-L1 expression levels on malignant NSCLC tumour and/or immune cells, and differences in antibodies and IHC platforms have raised questions about comparability among these assays and their diagnostic use.
In literature there is an increasing interest to evaluate the correlation between PD-L1 expression, response rate to PD-1/PD-L1 blockade therapy and additional potential biomarkers, from miRNA102,104,105 to complementary IHC assessment, with the aim of identifying a subgroup of patients with better ORR, PFS, and OS in immunotherapy regimens.
A recent study demonstrates that the PD-L1 IHC assessment in patients with Merkel carcinoma could be combined to integrative data such as PD-1 IHC expression profile of different cell types of the tumour microenvironment (TME), to obtain a more precise prediction of response to anti PD-L1/PD-1 antibodies 103.
In this study while the binomial presence or absence of PD-L1 expression in the TME was not sufficient to predict response to anti-PD-1 in patients with MCC, the quantitative assessments of PD-1+ and PD-L1+ cell densities as well as the geographic interactions between these two cell populations correlate with clinical response.
In literature, different studies report data of a small subgroup of patients with advanced NSCLC with minimal or no PD-L1 expression which present objective responses to PD-1/PD-L1 blockade therapy, in addition, other studies describe case of hyperprogressive disease, identified as a progression, according to RECIST criteria (Response Evaluation Criteria in Solid Tumors) at first control, with a tumour growth higher than 2-fold of the previous tumour growth, before the beginning of the immunotherapy.
[106-111] These data highlight the fragility of PD-L1 expression as a single reflection-marker of the intricate tumour microenvironment because it does not necessarily reflects the current T-cell response and PD-L1-cancer status.
One of the most interesting challenges in lung cancer landscape would be to find and validate a more precise and objective way to ensure a better selection of patients toward personalized medicine.
In this study we aim to evaluate different potential biomarkers that could predict the response to immunotherapy to better select patients.
In order to do so, we analyzed LDH levels and neutrophil to lymphocyte ratio (NLR) in whole blood samples prior of the treatment, PD-1 and PD-L1 IHC expression profile in Paraffin-embedded tissues.