Radiotherapy: An immune response modifier for immuno-oncology

Exploiting Radiation Therapy to Restore Immune Reactivity of Glioblastoma

“…For instance, radiation dose-dependent responses can be elicited on T-effector cells versus Tregs, macrophages, and TME regulation through TREX1-STING-IFN signaling (87,(125)(126)(127)(128). The optimal radiation dose and regimen together with the best sequencing between IT and RT remains elusive (19,129,130).…”

Immune radiobiology

“…The ability of IR to modulate host immune responses has been described forty years ago with seminal work from Stone who demonstrated that the efficacy of radiation therapy was dependent on the presence of T cells [ 1 ]. While these findings have been overlooked for a long-time, the advent of modern IT together with the growing evidence of the immunoadjuvant properties of IR has brought radiation therapy to the limelight [ 2 , 3 ].…”

“…The main concept is to exploit the immunogenic potential of IR to jumpstart host immune responses with the ultimate goal to raise the tail of cancer patient survival curves treated with immunotherapies [ 2 , 4 ]. The rationale for the use of IR as an immune adjuvant originates from extensive preclinical studies demonstrating that IR elicit an immunogenic cell death (ICD) and a type I interferon (IFN-I) response to generate antigen specific T cell killing [ 2 ].…”

“…The main concept is to exploit the immunogenic potential of IR to jumpstart host immune responses with the ultimate goal to raise the tail of cancer patient survival curves treated with immunotherapies [ 2 , 4 ]. The rationale for the use of IR as an immune adjuvant originates from extensive preclinical studies demonstrating that IR elicit an immunogenic cell death (ICD) and a type I interferon (IFN-I) response to generate antigen specific T cell killing [ 2 ]. These two non-mutually exclusive IR-induced biologic processes rely on (1) the coordinate release of damaged associated molecular pattern (DAMPs) molecules subsequent to oxidative endoplasmic reticulum (ER) stress; namely the surface exposure of calreticulin, the secretion of ATP and the release of high mobility group box 1 (HMGB1) [ 5 – 7 ] and (2) the activation of nucleic acid sensors pathways such as the CGAS/STING (cyclic GMP-AMP synthase/stimulator of interferon genes) and/or the retinoic acid inducible gene-I (RIG-I)-like receptors (RLRs) [ 8 – 10 ].…”

Immunological barriers to immunotherapy in primary and metastatic breast cancer

“…The realization that ICIs employed as stand‐alone immunotherapeutic agents are virtually ineffective in patients with BC has spun a considerable experimental effort aimed at the identification of combinatorial regiments that would unlock the therapeutic potential of ICIs. In multiple preclinical models of primary and metastatic BC, radiation therapy (RT) emerged as a promising combinatorial partner for ICI‐based immunotherapy (De Martino et al , 2021 ), driving the initiation of various clinical trials investigating RT plus ICIs in women with advanced or metastatic BC. Unfortunately, most of these studies document little, if any, advantage from combining RT with ICIs in patients with BC, even in the triple‐negative BC (TNBC) setting, in which the abundance of tumor‐infiltrating lymphocytes (TILs) has a major prognostic value (Voorwerk et al , 2019 ).…”