The EACR’s ‘Highlights in Cancer Research’ is a regular summary of the most interesting and impactful recent papers in cancer research, curated by the Board of the European Association for Cancer Research (EACR).
The list below appears in no particular order, and the summary information has been provided by the authors unless otherwise indicated.
Use the dropdown menu or ‘Previous’ and ‘Next’ buttons to navigate the list.
Whiteside, S.K. et al. Sci. Immunol. 8(90), peabo5558 (2023).
doi: doi.org/10.1126/sciimmunol.abo5558.
Summary of the findings
Summary of the findingsCancer immunotherapy has revolutionized the treatment of cancer. Breakthrough therapies, particularly those targeting immune checkpoints 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 tumors. However, clinical trials targeting Treg cells have had limited clinical efficacy prompting a deeper investigation into their role. Whiteside et al., demonstrated that that CD4+ Foxp3− conventional T (Tconv) cells acquire suppressive function upon depletion of Foxp3+ Treg cells, limiting therapeutic efficacy. Foxp3− Tconv cells within tumors adopt a Treg cell–like transcriptional profile upon ablation of Treg cells and acquire the ability to suppress T cell activation and proliferation ex vivo. Suppression was dependent on the immunosuppressive cytokine IL-10 and was enriched in Tconv cells expressing the chemokine receptor CCR8. Resistance to Treg cell depletion could be prevented through conditional deletion of Il10 in T cells or cotreatment with IL-10R blocking antibodies. This unexpected finding challenges the previous understanding that focusing solely on Treg cells could yield substantial therapeutic benefits.
Future impact
The study not only underscores the complexity of the immune system’s response to cancer but also opens new avenues for treatment. Acquisition of a Treg cell–like transcriptional profile by Tconv cells upon Treg cell ablation suggests that in practice there are very few molecules whose targeting will enable highly specific depletion of Treg cells within tumors. A question raised by this study is whether specific depletion of Treg cells is desirable rather than the targeting of molecules shared by Treg cells and cells with compensatory suppressive function induced upon Treg cell depletion. The research provides new targets for overcoming resistance to Treg depleting immunotherapies.
