Drawing a lung cancer map

What if genetic drivers of cancer could influence the composition and spatial organization of the tumour microenvironment? This is the question Logan Walsh, researcher at the Rosalind and Morris and Goodman Cancer Institute (GCI), and Dr. Philippe Joubert from l'Institut universitaire de cardiologie et de pneumologie de Québec addressed in their most recent study published in Nature Communications last September.

For Lung Cancer Awareness Month, we highlight this piece of research that pushes the boundaries of knowledge and leads the way for better treatment and outcomes for lung cancer patients.

Led by PhD candidate Saskia Hartner, the new study presents extensive profiling of 157 lung adenocarcinoma patient samples and uncovers significant differences between sub-groups. Lung adenocarcinoma is the most common lung cancer subtype, with limited treatment options and a high relapse rate, underscoring the urgent need for improved therapeutic strategies. They profiled each tumour samples using multiplexed imaging mass cytometry generating an extensive tumour atlas by integrating genomic and clinical data.

Driver mutations are often identified in lung adenocarcinoma patients and help guide treatment options. After characterization of genomic and clinical features of each patient, the research group profiled the composition of the tumour microenvironment by driver mutation subtype as well as sex and age. They uncovered significant differences in cancer and immune cell composition between oncogene driver subtypes.

Because of their high incidence in patients, Prof. Walsh and Dr. Joubert's research teams decided to focus on tumours driven by EGFR or KRAS mutations and investigate the impact of a co-mutation in the tumour-suppressor TP53. They found multiple cellular patterns within these oncogenic driver subgroups that were influenced by the presence or absence of TP53 co-mutation. When looking at cellular neighbourhoods, a method to determine which cell types are close together within the tumour, they identified neighbourhoods that were correlated with increased overall survival, such as the B-cell enriched neighbourhood. Further analysis uncovered an improved survival for patients with neighbourhood enriched in helper T cells, which is found more frequently in patients with EGFR mutations.

It was recently discovered that a TP53 co-mutation in EGFR can make some cancer treatments less effective, leading the research team to wonder how the immune landscape is different between the two genomic profiles and could lead to better tailored treatments. Looking back at the imaging mass cytometry data for cellular neighbourhoods, scientists found significant difference between single and co-mutation groups, such as loss of the helper T cell-enriched neighbourhood. They conclude that genomic alterations impact the spatial organization of the tumour and disease prognosis for the patient.

This new publication highlights how specific oncogenic drivers of lung adenocarcinoma specifically influence the immune and stroma cell population organizations, and, more importantly, how these characteristics can impact overall survival. It also points to the consequences of TP53 co-mutations on immune profile in the tumors as well as its cellular organization. Overall, the authors suggest that better clinical outcomes will arise from the integration of spatial immune parameters and genomic data from each patient, which will allow for better-suited treatments. This study was made possible with financial support from CIHR and FRQS and highlights the dedication of the GCI to improving outcomes for all patients, including ones affected by lung cancer.

Full article: Oncogenic driver mutations underlie the spatial tumour immune landscape of non-small cell lung cancer