Analysing patient biopsies collected from clinical trials across multiple tumour types has led to a deeper understanding of the mechanisms of immune response and escape. These studies have illustrated a range of immune involvement within the tumour microenvironment.1,2
The Roche research team has identified 3 primary immune phenotypes that describe the level of T-cell presence and activity within the tumour microenvironment, and can help determine disruptions or mechanisms of immune escape in cancer immunity.1-3
3 immune phenotypes characterise the pattern of immune activity1,2,4
- Immune desert
- Immune excluded
No existing cancer immunity: cancer immunity cycle cannot be initiated (disruptions in steps 1-3)1,2,5
- Absence of CD8+ T cells in the tumour microenvironment
- Lack of preexisting antitumour immunity
Immune escape mechanisms1-3
- Poor tumour immunogenicity due to low mutational load or lack of antigen release
- Tumour cells and immunosuppressive cells (regulatory T cells, myeloid-derived suppressor cells, etc), may inhibit dendritic cells from properly activating T cells
- Suboptimal T-cell activation due to disrupted costimulatory interactions
Cancer immunity halted: active T cells cannot reach tumour cells (disruptions in steps 4-5)1,2,5
- Abundance of immune cells in the tumour stroma
- Preexisting antitumour immunity rendered ineffective due to poor T-cell infiltration or retention
Immune escape mechanisms1,2
- High expression of receptors responsible for vasculogenesis and angiogenesis, such as VEGF
- Low levels of ligands for CXCR3, a chemokine receptor that plays a large role in T-cell trafficking
Cancer immunity held in check: active T cells in tumour microenvironment are not functioning properly (disruptions in steps 6-7)1-3
- Abundance of tumour-infiltrating immune cells, including CD4+ and CD8+ T cells
- Presence of proinflammatory and effector cytokines
- Higher mutational load
- Preexisting antitumour immunity is arrested
Immune escape mechanisms1,3
- Major histocompatibility complex not functioning normally or absent from cancer cells
- High expression of checkpoint markers, such as PD-L1
- Presence of immunosuppressive cells such as regulatory T cells and myeloid-derived suppressor cells
- Chen DS, Mellman I. Elements of cancer immunity and the cancer-immune set point. Nature. 2017;541:321-330. PMID: 28102259
- Kim JM, Chen DS. Immune escape to PD-L1/PD-1 blockade: seven steps to success (or failure). Ann Oncol. 2016;27:1492-1504. PMID: 272071083
- Hegde PS, Karanikas V, Evers S. The where, the when, and the how of immune monitoring for cancer immunotherapies in the era of checkpoint inhibition. Clin Cancer Res. 2016;22:1865-1874. PMID: 27084740
- Gajewski TF. The next hurdle in cancer immunotherapy: overcoming the non–T-cell–inflamed tumor microenvironment. Semin Oncol. 2015;42:663-671. PMID: 26320069
- Bacac M, Fauti T, Sam J, et al. A novel carcinoembryonic antigen T-cell bispecific antibody (CEA TCB) for the treatment of solid tumors. Clin Cancer Res. 2016;22:3286-3297. PMID: 26861458
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