Abstract
The need for predictive biomarkers that can accurately predict patients who will respond to immune checkpoint inhibitor (ICI) immunotherapies remains a clinically unmet need. The majority of research efforts have focused on expression of immune-related markers on the tumour and its associated tumour microenvironment (TME). However, immune response to tumour neoantigens starts at the regional lymph nodes, where antigen presentation takes place and is regulated by multiple cell types and mechanisms. Knowledge of the immunological responses in bystander lymphoid organs following ICI therapies and their association with changes in the TME, could prove to be a valuable component in understanding the treatment response to these agents. Here, we review the emerging data on assessment of immunological responses within regional lymph nodes as predictive biomarkers for immunotherapies.
Highlights
Immunotherapy, such as immune checkpoint inhibition (ICI), is used to treat several types of cancer including melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), head and neck cancers and some triple negative breast cancers (Borghaei et al, 2015; Larkin et al, 2015; Larkin et al, 2015; Le et al, 2015; Seiwert et al, 2016; Balar et al, 2017; Motzer et al, 2018; Schmid et al, 2020)
The human equivalent CD141+ CLEC-9A+ dendritic cells (DCs) have been found in tumour draining lymph node (TDLN) and were responsible for the cross presentation and activation of anti-tumour T cells in melanoma patients
CD86+ B cells in TDLN were associated with higher tumour grade and a greater number of metastatic lymph nodes
Summary
Immunotherapy, such as immune checkpoint inhibition (ICI), is used to treat several types of cancer including melanoma, renal cell carcinoma (RCC), non-small cell lung cancer (NSCLC), head and neck cancers and some triple negative breast cancers (Borghaei et al, 2015; Larkin et al, 2015; Larkin et al, 2015; Le et al, 2015; Seiwert et al, 2016; Balar et al, 2017; Motzer et al, 2018; Schmid et al, 2020). Specific genetic mutations in immune pathways, such as PD-1 and PD-L2 ligand gene chromosome 9p24.1 amplification (Green et al, 2010) and the patient’s HLA genotype encoding their MHC class 1 molecules, can determine the efficacy of the antitumour immune response following ICI therapy (Goodman and et al, 2020). Despite these numerous different biomarkers, none can be used to consistently predict response or as markers to reliably select ICI responsive patients across all tumour types. It is important to point out that it is believed the first step in a tumour immune response occurs within the primary tumour itself and is recognition of TABLE 1 | Summarising the studies investigating the importance of TDLN in anti-tumour immunity following immunotherapy
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