Finding your niche: immune evasion in quiescent tumor reservoirs

Abstract

Emerging immunotherapies offer a new hope for cancer patients but are not always effective even when a tumor is recognized by the immune system. Baldominos and colleagues address this challenge by characterizing a resilient niche of metabolically unique quiescent cancer cells (QCCs) that resist T cell-mediated control.

Figure 1.. Quiescent cancer cell niches can suppress immune function.

Breast cancer tumors can develop internal niches of proliferating (yellow, left) and quiescent (blue, right) cancer cells (QCC). QCCs show signs of higher Hif1a activity signatures, increased propensity for glucose uptake, and up-regulated expression of glycolytic enzymes with respect to their proliferating counterparts [3]. QCC regions show low CD8⁺ T cell infiltration with skewing towards the generation ofTex^TERM and away from Tex^PROG, as well as the presence of conventional dendritic cells (cDCs) with a decreased MHC-II and IFN signature. This immunosuppressive environment is associated with QCC resistance to T cell killing [3]. We speculate that glucose depletion and potential lactate release by the glycolytic QCC, as well as a direct effect of the hypoxic environment on immune cells might contribute to immunosuppression within QCC-niches. Tex^TERM, terminally exhausted T cell; Tex^PROG, progenitor exhausted T cell; cDC, conventional dendritic cell; Treg, regulatory T cell.