Immunotherapy not working?

▎WuXi AppTec Content Team Editor When it comes to malignant tumors, everyone's first reaction is that it is composed of a large number of cancer cells
.

But in reality, tumors are more like a community of many different types of cells, and in addition to cancer cells, tumors are also full of immune cells
.

Some immune cells are the tools our body uses to fight cancer, while others are used by cancer cells to evade pursuit
.

"Why does immunotherapy work for some cancer patients but not others?" said Matthew Krummel, a professor of pathology at the University of California, San Francisco.
"It's not just a question of who responds to therapy, our goal is to determine How many responses can targeted therapy produce?
"
And according to a new study in Cell, solving this question may first require a re-understanding of cancer classification
.

Cancers can be classified not only by their location, but also by the mode they are in.
Each type has its own unique cell composition and represents the unique survival mode of different tumors
.

The research team managed to obtain samples from more than 300 patients with tumors from different parts of the body, such as glioblastomas in the brain, lung adenocarcinomas in the lungs, melanomas in the skin, etc.
, thus showing different cancers difference between
.

Through the analysis of different tumor samples, including gene sequencing, cell imaging and surface marker classification, as well as clinical data analysis, the study divided the tumors into 12 groups based on the characteristics of the tumor microenvironment, which they called tumor prototypes
.

The immune cells and tumor-expressed genes contained in each group of tumor prototypes have unique patterns.
In addition to T cells, which are often of interest in immunotherapy, various immune cells such as macrophages, natural killer cells, and B cells are also found in different tumor prototypes.
have their own compositional differences
.

▲Schematic diagram of the research process (Image source: Reference [2]) However, we should not think that cancer tissues from the same site will be classified into the same tumor prototype
.

In fact, a group of tumor prototypes will contain multiple types of cancer.
For example, different types of melanomas are not in the same group.
Instead, a certain type of melanoma and a certain type of lung cancer have more similarities and will be classified as the same tumor prototype
.

In typing, the main factors considered are the activity of interferon-related signaling pathways and the imbalance between T cell and macrophage subsets
.

In addition, the cellular matrix is ​​also an important factor to be concerned about in trans-tissue tumors, and the abundance of CD8+ T cells and natural killer cells varies among tumor prototypes
.

Image source: 123RF This classification method is more accurate than the past to distinguish tumors by location.
Doctors can judge the best immunotherapy based on the tumor prototype in which a patient's cancer type is located, and predict how strongly they will respond to the therapy
.

"This classification allows us to eliminate misinformation in treatments that we may have been targeting cells that are completely absent in the tumor," Professor Krummel said
.

Notably, the entire study brought together 78 researchers and clinicians who provided strong interdisciplinary knowledge
.

Prof.
Krummel, who is planning to lead a team to conduct a more detailed analysis of tumor prototype classifications, pointed out that immunotherapy can be combined with corresponding tumor biological patterns, which in the future should be called tumor prototypes
.

Reference: [1] Sorting cancers by 'immune archetypes' represents potential new approach to developing precision immunotherapies.
Retrieved Jan 7th, 2022 from https://medicalxpress.
com/news/2022-01-cancers-immune-archetypes-potential- approach.
html[2] Alexis J.
Combes et al, Discovering dominant tumor immune archetypes in a pan-cancer census.
Cell, DOI: 10.
1016/j.
cell.
2021.
12.
004