Blood test identifies tumor neighborhoods impacting immunotherapy

Good news! Cancer is history (soon)! This could be a breakthrough!

"In brief

• Stanford Medicine researchers developed a blood test predicting tumor microenvironments that influence cancer treatment decisions and patient outcomes.
• The study identifies nine shared cellular neighborhoods across cancers, aiding understanding of tumor responses to immunotherapy and potential therapies.
• This noninvasive approach transforms cancer treatment strategies, allowing real-time monitoring of tumor evolution and enabling personalized therapeutic interventions.

A simple blood test can reveal the geographic relationships among healthy cells surrounding a cancerous tumor, researchers ... have found. The test is the first noninvasive way to study what’s called the tumor microenvironment, which plays a critical role in determining how different patients – even those with similar tumors – fare after diagnosis and treatment. ...

the researchers identified nine cellular neighborhoods, or spatial ecotypes, that cancers of all types share and 

some of which correlate with a tumor’s response to immunotherapy and a patient’s prognosis.

Because the blood test can be performed repeatedly, clinicians may soon have real-time access to information about which types of therapies are likely to be most successful. ...

The researchers studied more than 100 tumor specimens from 10 distinct types of cancer using the tools they had developed to map patterns of gene expression in nine cell types at varying locations throughout the tumor.

They identified nine distinct spatial ecotypes, or neighborhoods, each roughly the diameter of a human hair. They found that patterns of spatial ecotypes were conserved among all the tumors they studied; some ecotypes were more likely to occur at the border of the tumor and healthy tissue, while others were more likely found deeper inside the tumor, for example. Several of the newly identified ecotypes correlated with whether a tumor would respond to immunotherapy – suggesting they could help guide clinical decision-making. ..."

From the abstract:

"Multicellular programs in the tumour microenvironment (TME) drive cancer pathogenesis and response to therapy but remain challenging to identify and profile clinically.

Here, we present a machine-learning framework for multi-analyte profiling of spatially dependent cell states and multicellular ecosystems, termed spatial ecotypes (SEs).

By integrating over 10 million single-cell and spot-level spatial transcriptomes from diverse human carcinomas and melanomas, we identified nine SEs with broad conservation, each of which has unique biology, geospatial features and clinical outcome associations, including several linked to immunotherapy response.

Notably, SEs were distinguishable by DNA methylation profiling and were recoverable from plasma cell-free DNA (cfDNA) using deep learning.

In cfDNA from nearly 100 patients with melanoma, SE levels exhibited striking associations with immunotherapy response.

Our data reveal fundamental units of TME organization and demonstrate a multimodal platform for profiling solid and liquid TMEs, with implications for improved risk stratification and therapy personalization."

Blood test identifies tumor neighborhoods impacting immunotherapy | Stanford Report "A new study shows how a noninvasive blood test can identify nine tumor neighborhoods, predicting microenvironments that affect patient responses to immunotherapy."

Non-invasive profiling of the tumour microenvironment with spatial ecotypes (open access)

Nine cellular environments, or spatial ecotypes, are shown here in a melanoma tumor. Spatial ecotypes, defined by the cellular interactions and the gene expression patterns of their cells, give clues about effective treatment options.

Fig. 1: Multimodal profiling of SEs in human cancer.

Fig. 2: Geospatial map of multicellular programs across cancers.