Computational Program

We can now precisely map the locations of 100,000 cells within a tumor biopsy section and analyze the expression of 1,000 genes within each individual cell. This level of detail is comparable to obtaining a high-resolution spy satellite image of a battlefield, complete with audio recordings of every conversation each soldier has throughout the day. For instance, Figure 1 shows one of the first published datasets for a new spatial transcriptomics technology CosMx SMI which was obtained from a biopsy of non-small cell lung cancer (NSCLC). This single biopsy sample provides precise locations of 99,803 individual cells along with their identities and gene expression for approximately 1,000 probes (recently increased to 6,000 probes). By inspecting Fig. 1, clear examples of the structure of this “cancer battlefield” can be observed where the “front lines” occur on the edges of the cancer lesions (in tan) and the anti-cancer immune response is headquartered in the B-cell/T-cell clusters:

Our computational projects aim to deepen our understanding of the complex “battlefield” within tumors, where cancer cells and immune cells engage in a microscopic war. By employing advanced spatial transcriptomics, we can map these cells’ locations and activities with unprecedented detail, much like using high-tech surveillance to observe enemy movements on a battlefield. This approach will help identify the best drugs for patients who do not respond to standard therapies by revealing how cancer cells evade the immune system and suggesting new strategies for boosting the body’s own defenses.

In this exploration, we distinguish between beneficial and detrimental immune responses within the tumor microenvironment. Protective immune responses, often driven by adaptive immunity, are crucial as they involve cytotoxic T-cells and B-cell reactions that directly target and destroy cancer cells. Conversely, regenerative immune responses, typically orchestrated by innate immunity, involve tissue-resident macrophages, neutrophils and fibroblasts that facilitate tissue repair but can sometimes foster cancer progression if dysregulated. Understanding these contrasting roles enhances our ability to manipulate immune actions, potentially transforming a harmful response into a therapeutic ally against cancer.