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.
Monteran, L. et al. Cancer Discovery. 625, 14: 1252–75 (2024).
doi: 10.1158/2159-8290.CD-23-0762.
Summary of the findings
Summary of the findingsBone is the most frequent site of breast cancer metastasis leading to severe morbidities. Although immunotherapies have revolutionized the treatment of several cancer types, their efficacy in treating breast cancer metastasis is still limited, and bone metastasis remain incurable. This study profiled the changes in the immune microenvironment during bone metastatic progression and characterized the crosstalk between immunosuppressive granulocytes (myeloid-derived suppressive cells; MDSCs) and dysfunctional cytotoxic T lymphocytes (CTLs).
.
Using an immunocompetent mouse model of spontaneous breast cancer bone metastasis, the authors found that bone metastatic lesions are infiltrated by MDSCs and PD-1 and TIGIT-expressing dysfunctional CTLs. Temporal transcriptome analysis revealed extensive communication between MDSCs and T cells via their expression of immune checkpoint molecules. The authors further identified IL1b as a key driver of immune suppression in granulocytes: targeting IL1b in vivo by neutralizing antibodies, or by BM transplantation from IL1b KO mice reduced MDSC accumulation and inhibited their immunosuppressive phenotype, restoring T cell killing activity. Importantly, TIGIT was shown to be expressed in human bone metastasis from various cancer types.
Using an immunocompetent mouse model of spontaneous breast cancer bone metastasis, the authors found that bone metastatic lesions are infiltrated by MDSCs and PD-1 and TIGIT-expressing dysfunctional CTLs. Temporal transcriptome analysis revealed extensive communication between MDSCs and T cells via their expression of immune checkpoint molecules. The authors further identified IL1b as a key driver of immune suppression in granulocytes: targeting IL1b in vivo by neutralizing antibodies, or by BM transplantation from IL1b KO mice reduced MDSC accumulation and inhibited their immunosuppressive phenotype, restoring T cell killing activity. Importantly, TIGIT was shown to be expressed in human bone metastasis from various cancer types.
.
Finally, co-targeting IL1b and TIGIT reactivated anti-tumor immunity, and enhanced survival in mice with bone metastasis, suggesting that combinatorial targeting of IL1b and TIGIT may be a novel approach to treat bone metastasis.
Finally, co-targeting IL1b and TIGIT reactivated anti-tumor immunity, and enhanced survival in mice with bone metastasis, suggesting that combinatorial targeting of IL1b and TIGIT may be a novel approach to treat bone metastasis.
.
Future impact
Developing new immunotherapeutic strategies to treat breast cancer bone metastasis is an urgent need, as breast cancer is the most common malignancy in women in the Western world. Targeting the immunosuppressive microenvironment while stimulating anti-tumor immunity presents a promising avenue for expanding classical treatment options. The findings of this study highlight the importance of finding the delicate balance between inhibiting immunosuppressive cells and promoting anti-tumor immunity, offering new insights for combating bone metastatic disease.
.
