Dear Editor,

T cells recognize and eliminate cancer cells. Prolonged survival of cancer patients is associated with not only intratumoral T cell infiltration but also the functional status of infiltrated T cells (Galon and Bruni, 2020). The immune contexture, including the number and functionality of T cells, is modulated by the tumor microenvironment (Joyce and Fearon, 2015; Galon and Bruni, 2020). The tumor microenvironment regulates the recruitment and accumulation of T cells, as well as the local activation, replication, and viability of T cells within tumors (Joyce and Fearon, 2015). Dynamic remodeling of the extracellular matrix (ECM) microenvironment, including basement membranes (BMs) underneath epithelial and endothelial cells, is one of the characteristics of cancer. ECM regulates immune cell adhesion and migration, and thus modulates inflammation in the tumor microenvironment, in addition to regulating cancer cell proliferation, migration, and invasion. T cells migrate poorly in dense collagen matrix areas surrounding tumor nests (Salmon et al., 2012; Joyce and Fearon, 2015). The resultant T cell trapping in the collagen matrix and exclusion from the tumor mass attenuate antitumor immunity and the efficacy of immune therapies (Salmon et al., 2012; Joyce and Fearon, 2015). Reduction of the collagen matrix density increased intratumoral T cell infiltration (Mariathasan et al., 2018; Peng et al., 2020; Nicolas-Boluda et al., 2021). However, it had minimal effect on tumor growth but improved the response to anti-PD-1 therapy (Mariathasan et al., 2018; Peng et al., 2020; Nicolas-Boluda et al., 2021), suggesting that infiltrated T cells were not properly functioning. Other factors, including the intratumoral ECM, may modulate T cell functionality in tumors.