The tumor microenvironment confers profound resistance to anti-cancer immunotherapy. By targeting LIGHT, a member of the TNF superfamily of cytokines, to tumor vessels via a vascular targeting peptide (VTP), we developed a reagent with the dual ability to modulate the angiogenic vasculature and to induce tertiary lymphoid structures (TLSs). LIGHT-VTP triggered the influx of endogenous T cells into autochthonous or syngeneic tumors, which are resistant to immunotherapy. LIGHT-VTP in combination with checkpoint inhibition generated a large number of intratumoral effector and memory T cells with ensuing survival benefits, while the addition of anti-tumor vaccination achieved maximal therapeutic efficacy. Thus, the combination treatments stimulated the trafficking of pre-existing endogenous effector T cells as well as their intratumoral activation and were more successful than current immunotherapies, which fail due to tumor-intrinsic resistance mechanisms.

Mast cells affect growth in various humanCancer growth is dependent on the reciprocal interaction between tumor cells and their microenvironment. Cancerassociated fibroblasts, 1 vascular cells, and inflammatory cells such as macrophages [2][3][4] have been shown to promote prostate tumor growth. Mast cells are also of importance for tumor growth and have been shown to affect angiogenesis 5-7 but are also potent regulators of inflammation and thus their specific function during tumor progression is complex and shows significant plasticity. 8 -10 Their role in prostate cancer (PC) in patients was recently explored in two separate studies using tryptase and c-Kit as markers for mast cells. These studies lacked the discrepancy between intra-and peritumoral mast cells and did not identify mast cells as independent prognostic variables. One of the studies showed that tryptase-positive mast cells were related to poor outcome in PC patients. 12 The other study analyzed c-Kit-positive cells in tumor samples from PC patients and found an association between increased mast cell numbers and a favorable prognosis. 13Castration therapy is the gold standard for treatment of patients with metastatic PC, but in the majority of cases the formation of castrate-resistant prostate tumors is inevitable. The mechanisms behind the relapse are not fully understood but could be related to changes in the androgen receptor and the tumor stroma.

Since James Scott introduced the concept of ‘everyday resistance’ in 1985, research has grown within partly overlapping fields. Existing studies utilize very different definitions, methodologies and understandings of ‘everyday resistance’, which makes a systematic development of the field difficult. In previous work, the authors have suggested a theoretical and definitional framework where everyday resistance is understood as a specific kind of resistance that is done routinely yet is not publicly articulated with political claims or formally organized. A more comprehensive and systematic exploration of this challenging phenomenon is possible through an analysis where: repertoires of everyday resistance are taken into account, together with relations between actors, as well as the spatialization and temporalization of resistance. These analytical dimensions are explained and motivated through illustrations from existing research. Finally, it is argued all four dimensions need to be studied in intersections.