Home » News & Articles » 2023 » Finding new ways to improve cancer immunotherapies: rethinking Treg cell targeting

Finding new ways to improve cancer immunotherapies: rethinking Treg cell targeting

New study co-authored by King’s CRA Dr Sarah Whiteside explores how conventional CD4+ T cells hinder cancer immunotherapies targeting Treg cells.
swhiteside

In recent years, cancer immunotherapy has emerged as a revolutionary approach for treating advanced cancers. Breakthrough therapies, particularly those targeting immune checkpoints like PD-1 and CTLA-4, have transformed the outlook for many cancer patients. However, not all patients respond to these treatments.

Regulatory T (Treg) cells are powerful immunosuppressive cells which limit a patient’s immune response to cancer. As a consequence, targeting Treg cells has been a focus for researchers seeking to enhance immune responses against tumours. However, clinical trials targeting Treg cells have thus far been underwhelming, prompting a deeper investigation into their role.

A new study by researchers from the University of Cambridge Department of Pathology, led by senior author Prof. Rahul Roychoudhuri and first author Dr Sarah Whiteside, sheds light on the complex dynamics between Treg cells and cancer. The study, titled 'Acquisition of suppressive function by conventional T cells limits anti-tumor immunity upon Treg depletion', reveals a previously unrecognized source of immune suppression which occurs following therapeutic depletion of Treg cells, limiting response efficacy.

“The findings unveil a compensatory mechanism where conventional T cells acquire suppressive functions, limiting the effectiveness of therapies targeting Treg cells. This insight is crucial for developing more effective cancer immunotherapies which work by depleting Treg cells" said Prof. Roychoudhuri about the study findings.

The research team used cutting-edge cellular and molecular immunology approaches and cancer models to demonstrate that upon therapeutic depletion of Treg cells, a subset of conventional T cells, marked by expression of the chemokine receptor CCR8 adopt Treg cell-like behaviour, producing an immunosuppressive cytokine IL-10 which subsequently limits the efficacy of the immune response released upon Treg repletion. This unexpected finding challenges the previous understanding that focusing solely on Treg cells could yield substantial therapeutic benefits.

Sarah Whiteside, the study's first author, emphasizes the broader implications of their work: 

By recognizing the compensatory immunoregulatory functions taken up by Tconv cells when Treg cells are depleted, we can explore new strategies that target these cells alongside Treg cells to enhance the efficacy of cancer treatments. As cancer treatment continues to evolve, the findings represent a significant step forward in understanding and potentially overcoming the limitations of current immunotherapies.

The study not only underscores the complexity of the immune system's response to cancer but also opens new avenues for cancer treatment. By identifying the role of interleukin (IL)-10-expressing CCR8+ Tconv cells in mediating immune suppression, the research provides a new targets for overcoming immunotherapy resistance to Treg depleting immunotherapies. The implications of this study are significant, offering hope for improved therapies for cancer patients who currently do not benefit from existing treatments.

The research was conducted at the University of Cambridge Department of Pathology and the CRUK Cambridge Cancer Centre in collaboration with the research group of Dr Enrico Lugli at Humanitas in Milan (Italy). The research was conducted with support from the UK Medical Research Council and an ERC Consolidator Award to Prof Roychoudhuri.

Sarah Whiteside was a College Research Associate and member of Professor  Roychoudhuri’s research group from 2018 to 2023 and has just taken up a new position in the US in December 2023

Similar Entries

img_20220202_102542_hdrcrop

King's CRAs working together to fight cancer

Kerrie McNally and Tiphaine Douanne are combining their expertise to gain new insights into the role of protein trafficking in T cells.

1

New study shows ‘biodiversity boost’ planning policy needs to improve metric to reflect the intricacies of ecosystems

Research Fellow Cicely Marshall hopes the results of her study will help improve the way nature’s value is calculated and translate into real-life gains for birds and butterflies as the UK plans to build 300,000 homes a year by mid-2020.
t_cell

New research from King's Fellow sheds light on killer T cells

Gillian Griffiths and her team have discovered how T cells are able to replenish their ability to destroy cancer cells.

dtwstn_wwairekt

Recent graduate wins Clinical Medicine Prize

Oisín Huhn has been awarded the Milo Keynes Prize for his PhD thesis.

New Entrepreneur-in-Residence arrives at King's

Co-Founder of Owlstone, Billy Boyle, will be available to students interested in creating their own start-ups

29-3-23

Research into ‘mini placentas’ gives new insights into human pregnancy

A new study from King's Fellow Ashley Moffett and her colleagues has mapped the complete trajectory of placental development.

mini-placenta

‘Mini-placentas’ help scientists understand the causes of pre-eclampsia and pregnancy disorders

King’s Fellow Ashley Moffett and colleagues have grown ‘mini-placentas’ in the lab and used them to shed light on how the placenta develops and interacts with the inner lining of the womb.

eir_scholars

Meet the two new Entrepreneur-in-Residence MPhil students

Kai Hu and Pallavi Goel are this year’s Entrepreneur-in-Residence MPhil students, supported by the generous donation from the College’s first Entrepreneur-in-Residence, Sheryl Cuisia.

Follow us on Instagram

View more