9MO - Profile of immunorecognition related markers including HLA-1 expression to predict response to immunocheckpoint inhibitors in non-small cell lung cancer

Background

The incorporation of immunotherapy (IT) with immune-checkpoint inhibitors (ICIs) into clinical practice has represented a major breakthrough in non-small cell lung cancer (NSCLC) treatment, particularly in cases where the cancer has no druggable genetic alterations. The human histocompatibility complex (HLA-1) is essential for antigen presentation capability and immune response. Here we evaluate HLA-1 and other immune-related markers as potential predictive factors of response to ICI in NSCLC.

Methods

We evaluated the immunophenotype in a cohort of 140 metastatic NSCLC patients who received treatment with ICI based regimens for metastatic setting at ICO Badalona from 2014 to 2019. We profiled the expression levels by immunohistochemistry (IHC) of HLA-1, and other immune-related markers including CD73, CD8, and PD-L1 (Ventana SP263) from formalin-fixed paraffin-embedded (FFPE) human tissue samples. We evaluated the response and clinical outcomes to ICI. The Chi-Square test for categorical variables and Kaplan Meier method for survival analysis were performed.

Results

In our cohort of 140 patients: 86% males and 14% females, 63% were lung adenocarcinomas (LuAD) and 37% squamous cell carcinoma (SCC). They received IT treatment as a 1st line (29%), 2nd (46%), and 3rd or further lines (25%). PD-L1≥50% was present in 25% of cases. 67 patients were evaluable for HLA-1 at the moment of the analysis. Our work reveals that ∼45% of NSCLC in our cohort express low staining levels of HLA-1 (down regulation or total absence) compared to normal/high staining (55%). Those patients present worse clinical outcomes: mPFS to IT 9.1 (6.5–20.2) vs 21 (13.9-NR) months (p-value 0.028), respectively. We also report that HLA-1 is co-expressed with PD-L1 (p <0.005), regardless of histological subtype.

Conclusions

Down-regulation of HLA-1 expression is a mechanism of immune-evasion and affects a subset of NSCLC, which abrogates the response to ICI. HLA-1 IHC is an emerging immunomarker in NSCLC and predictor of response to ICI. In addition, we observed that HLA-1 is co-expressed with PD-L1 and represents a surrogate marker of immune-inflamed phenotype which might predict better outcomes to PD(L)-1 blockade.

Legal entity responsible for the study

The authors.

Funding

Merck Serono, SEOM (Sociedad Española de Oncología Médica).

Disclosure

All authors have declared no conflicts of interest.