NSCLC Biomarkers to Predict Response to Immunotherapy with Checkpoint Inhibitors (ICI): From the Cells to in-Vivo Images

Abstract

Lung cancer remains the leading cause of cancer-related death and it is usually diagnosed in advanced stages (stage III or IV). Recently, the availability of targeted strategies and of immunotherapy with checkpoint inhibitors (ICI) has favorably changed patient prognosis. Treatment outcome is closely related to tumor biology and interaction with the host immune microenvironment (TME). Whether for targeted therapies the response relies on the presence of specific genetic alterations in tumor cells, for ICI accurate biomarkers of response are lacking and clinical outcome likely depends on multiple factors, host and tumor-related. This paper is an overview of the ongoing research on predictive factors both from in-vitro/ex-vivo analysis (ranging from conventional pathology to molecular biology) and in-vivo analysis, where molecular imaging is showing an exponential growth and use due to the technological advancement and to the new bioinformatics approaches applied to image analyses that allow specific features recovery in specific tumor subclones.

Cancer relevance of circulating antibodies against LINE-1 antigens in humans

“…4) (Seidel et al, 2018;Vaddepally et al, 2020). The lack of reliable predictive tests for defining subsets of patients capable of responding to immunotherapy is a significant clinical problem (Liberini et al, 2021;Filipovic et al, 2020). In the context of our hypothesis, high levels of anti-L1 IgG mean that the immune system "senses" the tumor but cannot effectively eradicate it, suggesting the potential for a high probability of success utilizing immunotherapy by immune checkpoint inhibitors.…”

Immunotherapeutic targets in non‐small cell lung cancer

“…The TMB cutoffs varied markedly between cancer types; for instance, a high TMB cutoff for NSCLC was 13.8 mut/Mb [190]. the FDA approved Pembrolizumab use in patients who suffer from advanced solid cancers with high TMB (≥10 mutations per mega base evaluable with the MSK‐IMPACT or the FoundationOne CDx analyses), based on the rates of overall response from a pre‐planned retrospective study from the KEYNOTE‐158 trial taking place in June 2020 [191, 192].…”

“…MDSCs proliferate during chronic infection and cancer and have been shown to inhibit NK cell and T cell activity [136,137]. MDSCs have been shown to have a negative predictive role for ICI outcome in melanoma cancer [138,139].…”