The immunogram of inflammatory breast cancer

Carmine Valenza; Dario Trapani; Nicola Fusco; Xiaoping Wang; Massimo Cristofanilli; Naoto T Ueno; Giuseppe Curigliano

doi:10.1016/j.ctrv.2023.102598

The immunogram of inflammatory breast cancer

Cancer Treat Rev. 2023 Sep:119:102598. doi: 10.1016/j.ctrv.2023.102598. Epub 2023 Jul 8.

Authors

Carmine Valenza¹, Dario Trapani¹, Nicola Fusco², Xiaoping Wang³, Massimo Cristofanilli⁴, Naoto T Ueno⁵, Giuseppe Curigliano⁶

Affiliations

¹ Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy.
² Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy; Division of Pathology, IEO, European Institute of Oncology, IRCCS, Milan, Italy.
³ The University of Texas MD Anderson Cancer Center, Department of Breast Medical Oncology, Houston, TX, USA.
⁴ Division of Medical Oncology, Internal Medicine Department, Weill Cornell Medicine, New York, NY, USA.
⁵ University of Hawai'i Cancer Center, Honolulu, HI 96813, USA.
⁶ Division of New Drugs and Early Drug Development for Innovative Therapies, European Institute of Oncology, IRCCS, Milan, Italy; Department of Oncology and Hemato-Oncology, University of Milan, Milan, Italy. Electronic address: giuseppe.curigliano@ieo.it.

PMID: 37437342
DOI: 10.1016/j.ctrv.2023.102598

Abstract

Inflammatory breast cancer (IBC) is the most aggressive and fatal clinical presentation of breast cancer. Despite the term "inflammatory", based on the clinical presentation, IBC is biologically driven by an immunosuppressive tumor microenvironment (TME). Whether IBC can be switched into an immune-inflamed TME by immune-checkpoint inhibitors (ICIs) is a matter of debate. Presently, measurable biomarkers of IBC-TME have never been synthetized into a comprehensive portray of the immune-milieu (i.e., an immunogram), describing the immune-vulnerability of IBC and potentially predicting the response to ICIs. We propose an immunogram for IBC, based on preclinical and clinical studies, including six parameters: the presence of immune-effector cells, of immune-suppressive cells and of immune checkpoints, the general immune status, the activation of immune-suppressive pathways, the tumor foreignness. The IBC immunogram suggests the existence of a preexisting immune TME that is suppressed by mechanisms of immune-escape but might be restored by ICIs. The combination of chemotherapy and ICIs in patients with IBC is based on a strong biological rationale. However, the design and the development of clinical trials assessing the incorporation of ICIs raise many methodological and practical issues. In parallel with the further comprehension of IBC biology, the prospective validation and integration of biomarkers predictive of response to ICIs are warranted.

Keywords: Biomarkers; Immune-checkpoint inhibitors; Immunogram; Inflammatory breast cancer.

Publication types

Review