Improving efficacy of cancer immunotherapy through targeting of macrophages

ABSTRACT

T cell-based immunotherapies have revolutionized the treatment against cancer. But complete and long-lasting efficacy is only observed in a fraction of the patient population. One of the suspected causes is the inability of cytotoxic T cells, endowed with tumor killing ability, to reach their malignant targets. Using dynamic fluorescence imaging to study the dynamic of T cells in tumors from patients with lung cancer, we have recently demonstrated that macrophages trap the T lymphocytes, which are not longer able to contact the tumor cells. In murine models of breast cancer, we could show that the depletion of macrophages allows T cells to interact with tumor cells, a process which enhances anti-PD-1 immunotherapy. These findings illustrate the relevance of current clinical trials combining a strategy that deplete or modulate macrophages with anti-PD-1 immunotherapy.

Keywords:

• Cancer
• T cells
• immunotherapy
• migration
• macrophages
• anti-PD-1

Abbreviations

CAF	=	carcinoma-associated fibroblasts
CAR	=	chimeric antigen receptor
CSF1R	=	colony stimulating factor 1 receptor
ECM	=	extracellular matrix
TAM	=	tumor-associated macrophages

Disclosure of potential conflicts of interest

No potential conflict of interest was reported by the authors.

Additional information

Funding

Our work is supported by grants from the French Ligue Nationale contre le Cancer (Equipes labellisées), Plan Cancer (Tumor heterogeneity and ecosystem program) (ED), AIRC (EP), CARPEM (Cancer Research for Personalized Medicine) (EP) and Fondation de France (EP).