Why do some immune cells become powerful disease fighters while others do not?

Salerno wants to understand what happens inside a T cell as it acquires its function. In particular, she wants to discover how signals from the cell’s surroundings trigger internal changes that determine the specific role it takes on.

By uncovering the molecular mechanisms behind this process, she hopes to find new ways to guide immune responses more precisely, and ultimately improve vaccines and cancer treatments.

One cell, many ways to fight

Our immune system has to respond to many different threats, from viruses and other pathogens to cancer. Each threat presents a different challenge, so the immune response must be tailored accordingly.

CD4 T cells, a specific group of T cells, help coordinate this response. Some CD4 T cells help other immune cells attack infected or cancerous cells, while others help the production of antibodies. Choosing the right role is essential for fighting infections, generating effective responses to vaccines and controlling cancer.

Understanding the molecular logic

But how does a CD4 T cell know which function to take on? Part of the answer lies in the signals the cell receives from its surroundings. These external signals must be converted into a series of molecular changes inside the cell that shape its behavior and function.

This is where Salerno's research comes in. “I want to understand how immune cells acquire their function and what allows them to continue working effectively. If we can crack that code, we can learn how to guide immune responses with greater precision”, says Salerno.

Fundamental knowledge to improve human health

To answer these questions, Salerno focuses on a crucial step between receiving a signal and developing a specific function: protein production. Proteins are the working parts of a cell: they carry out most of its tasks and determine how it behaves. Changing which proteins are produced can therefore transform what an immune cell does.

A key part of this process involves RNA. RNA molecules are temporary messages containing instructions for making proteins. A cell do not use every RNA message equally or at the same time. Instead, it carefully control which messages are used and how much protein is made from each one.

Salerno wants to understand how T cells make these choices and how the signals they encounter influence them. “Revealing these rules could eventually help us steer immune cells towards the functions needed to fight disease more effectively.”

Why does this matter for a disease like cancer?

Understanding how T cells acquire and maintain their functions could have implications for many diseases. In cancer, for example, CD4 T cells that should help the immune system attack a tumor can lose their protective function. This loss makes it more difficult for the immune system to control tumor growth. If researchers understand why this happens, they could find new ways to guide them back towards a more protective state.

Vaccines present another opportunity, as they aim to trigger specific immune responses. Better understanding how signals determine the function of T cells could eventually help researchers investigate whether this response can be guided more precisely. The same fundamental knowledge could also be relevant to infectious and autoimmune diseases.

Salerno’s work is fundamental by nature, and therefore not directly aimed at developing new treatments. First, she wants to understand exactly how these processes work inside immune cells. In the longer term, however, this knowledge could open up new ways of making better use of our immune system, contributing to the generation of more effective vaccines or new forms of cancer immunotherapy.

Building a new team and combining different techniques

The ERC Starting Grant will allow Salerno to establish a new line of research and expand her team. Her work will combine expertise from immunology and RNA biology to tackle questions that could not be addressed through either field alone. “This grant gives me the freedom to build a multidisciplinary team, with talented young scientists working alongside me to investigate an ambitious question that is very close to my heart. It allows us to explore scientific directions that would otherwise be difficult to pursue.”

Salerno’s team will combine different research models and techniques, including mouse models, human cells and tumor tissue from patients. By linking these with detailed molecular analyses, they can examine the same biological question from different perspectives and uncover what happens inside individual CD4 T cells.

Reprogramming immune response is ultimate goal

The immediate aim of this research is to uncover the rules that determine which RNA messages a T cell uses to produce proteins and acquire its specific functions. Reprogramming immune responses remains a longer-term ambition. “My ultimate goal is to understand the language of RNA translation well enough to learn how we might reprogram an immune response.”

Achieving that goal will require many steps. But by revealing the fundamental workings of immune cells, Salerno and her team hope lay the foundation for new ways to harness the immune system and improve human health.