Macrophage targeting: opening new possibilities for cancer immunotherapy

Luca Cassetta, Takanori Kitamura

Research output: Contribution to journalReview articlepeer-review

Abstract / Description of output

Tumour‐infiltrating immune cells regulate the tumour development and progression either negatively or positively. For example, cytotoxic lymphocytes (CTL) such as CD8+ T and natural killer (NK) cells can recognize and eliminate cancer cells, and thereby restrict the tumour growth and metastasis, if they exert full cytotoxicity. In contrast, tumour‐infiltrating myeloid cells such as tumour‐associated macrophages (TAM) promote the expansion and dissemination of cancer cells depending on their functional states. Given the tumour killing ability of CTL, the augmentation of CTL‐induced anti‐tumour immune reactions has been considered as an attractive therapeutic modality for lethal solid tumours and several promising strategies have emerged now, which include immune checkpoint inhibitors, cancer vaccines and adoptive CTL transfer. These immunotherapies are now tested in clinical trials and have shown significant anti‐tumour effects on patients with lymphoma and some solid tumours such as melanoma and lung cancer. Despite these encouraging results, so far these therapies are not efficient in a certain fraction of patients and tumour types by tumour‐cell‐intrinsic mechanisms such as the impaired antigen presentation and/or tumour‐cell‐extrinsic mechanisms including the accumulation of immunosuppressive cells. Several animal studies suggest that tumour‐infiltrating myeloid cells, especially TAM, are one of the key targets to improve efficacy of the immunotherapies since these cells can suppress functions of CD8+ T and NK cells. In this review, we will summarize recent animal studies regarding the involvement of TAM in the immune checkpoint, cancer vaccination, and adoptive CTL transfer therapies, and discuss the therapeutic potential of TAM targeting to improve the immunotherapies.
Original languageEnglish
JournalImmunology
Early online date2 Jul 2018
DOIs
Publication statusE-pub ahead of print - 2 Jul 2018

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