The molecular basis of immuno-radiotherapy

Koukourakis, Ioannis M; Tiniakos, Dina; Kouloulias, Vassilis; Zygogianni, Anna

doi:10.1080/09553002.2023.2144960

Cited by 6 publications

(7 citation statements)

References 194 publications

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“…While there may be an advantage for combined treatment with radiotherapy and immune checkpoint blockade in some types of cancer, some clinical trials fail to show a superior effect of radiotherapy in combination with immune checkpoint blockade compared with radiotherapy plus chemotherapy or molecular-targeted therapy [323][324][325][326]. Treatment of patients with locally advanced-squamous cell carcinoma of head and neck by pembrolizumab in combination with radiotherapy fails to improve the tumor control and survival compared with the cetuximab (anti-EGFR monoclonal antibody)-radiotherapy arm, while the toxicity appears to be less in the pembrolizumab-radiotherapy arm [326].…”

Section: Clinical Testing Of Cancer Therapy Involving Rlrs Activationmentioning

confidence: 99%

Exploiting RIG-I-like receptor pathway for cancer immunotherapy

et al. 2023

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RIG-I-like receptors (RLRs) are intracellular pattern recognition receptors that detect viral or bacterial infection and induce host innate immune responses. The RLRs family comprises retinoic acid-inducible gene 1 (RIG-I), melanoma differentiation-associated gene 5 (MDA5) and laboratory of genetics and physiology 2 (LGP2) that have distinctive features. These receptors not only recognize RNA intermediates from viruses and bacteria, but also interact with endogenous RNA such as the mislocalized mitochondrial RNA, the aberrantly reactivated repetitive or transposable elements in the human genome. Evasion of RLRs-mediated immune response may lead to sustained infection, defective host immunity and carcinogenesis. Therapeutic targeting RLRs may not only provoke anti-infection effects, but also induce anticancer immunity or sensitize “immune-cold” tumors to immune checkpoint blockade. In this review, we summarize the current knowledge of RLRs signaling and discuss the rationale for therapeutic targeting RLRs in cancer. We describe how RLRs can be activated by synthetic RNA, oncolytic viruses, viral mimicry and radio-chemotherapy, and how the RNA agonists of RLRs can be systemically delivered in vivo. The integration of RLRs agonism with RNA interference or CAR-T cells provides new dimensions that complement cancer immunotherapy. Moreover, we update the progress of recent clinical trials for cancer therapy involving RLRs activation and immune modulation. Further studies of the mechanisms underlying RLRs signaling will shed new light on the development of cancer therapeutics. Manipulation of RLRs signaling represents an opportunity for clinically relevant cancer therapy. Addressing the challenges in this field will help develop future generations of cancer immunotherapy.

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Section: Clinical Testing Of Cancer Therapy Involving Rlrs Activationmentioning

confidence: 99%

Exploiting RIG-I-like receptor pathway for cancer immunotherapy

et al. 2023

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“…Systemic immune response and modulation after CRT may play an important role in the intratumoral immune response. For example, FOLFOX chemotherapy enhances CD8-mediated cytotoxic response in colorectal tumors [74], and RT induced-radio-vaccination triggers a large cascade of immune responses that may overcome the adverse role of PD-L1 expression [2].…”

Section: Prognostic Relevancementioning

confidence: 99%

“…Loss of HLA-class-I molecules expression, which can be attributed to epigenetic pathways and the mutations of genes involved in the HLA-class-I complex formation, is a process that malignant cells utilize to evade immune-surveillance [96]. Experimental and clinical studies suggest that cancer cell irradiation upregulates HLA-class-I molecules, which may prove important in immuno-RT combinations [2,97,98]. Furthermore, cancer cells suppress HLA-class-I expression during IO, leading to immuno-resistance, while their re-expression after RT can restore IO efficacy in experimental models [99].…”

Section: Hla-class-i Moleculesmentioning

confidence: 99%

“…Tumor antigens activate dendritic cells that educate T-cells to elicit antigen-specific cytotoxic responses. Cytokines and chemokines, secreted by cancer cells, trigger innate and adaptive immune responses, also acting as chemotactic stimuli to attract inflammatory cells in the tumor environment [2].…”

Section: Introductionmentioning

confidence: 99%

“…Given the rapid incorporation of new IO drugs in the already established practice, potential synergistic combinations between RT and IO are being explored. The immuno-modulatory (immunogenic cell death and radio-vaccination) effects of RT have been under investigation since the first decades of the 20th century [2]. Understanding these interactions between RT and the immune system would be a significant step towards the more effective utilization of both treatment modalities.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Immune Response and Immune Checkpoint Molecules in Patients with Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy: A Review

Koukourakis

Platoni

Tiniakos

et al. 2023

CIMB

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It is well-established that tumor antigens and molecules expressed and secreted by cancer cells trigger innate and adaptive immune responses. These two types of anti-tumor immunity lead to the infiltration of the tumor’s microenvironment by immune cells with either regulatory or cytotoxic properties. Whether this response is associated with tumor eradication after radiotherapy and chemotherapy or regrowth has been a matter of extensive research through the years, mainly focusing on tumor-infiltrating lymphocytes and monocytes and their subtypes, and the expression of immune checkpoint and other immune-related molecules by both immune and cancer cells in the tumor microenvironment. A literature search has been conducted on studies dealing with the immune response in patients with rectal cancer treated with neoadjuvant radiotherapy or chemoradiotherapy, assessing its impact on locoregional control and survival and underlying the potential role of immunotherapy in the treatment of this cancer subtype. Here, we provide an overview of the interactions between local/systemic anti-tumor immunity, cancer-related immune checkpoint, and other immunological pathways and radiotherapy, and how these affect the prognosis of rectal cancer patients. Chemoradiotherapy induces critical immunological changes in the tumor microenvironment and cancer cells that can be exploited for therapeutic interventions in rectal cancer.

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Anti-PD-1 immunotherapy with dose-adjusted ultra-hypofractionated re-irradiation in patients with locoregionally recurrent head and neck cancer

2023

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Introduction Patients with recurrent inoperable squamous-cell head-neck cancer (HNSCC) after chemo-radiotherapy have an ominous prognosis. Re-irradiation can be applied with some efficacy and high toxicity rates. Anti-PD-1 immunotherapy is effective in 25% of patients. Immunogenic death produced by large radiotherapy (RT) fractions may enhance immune response. Materials and methods We evaluated the efficacy and tolerance of ultra-hypofractionated immuno-radiotherapy (uhypo-IRT) in 17 patients with recurrent HNSCC and 1 with melanoma. Four of HNSCC patients also had oligometastatic disease. Using a dose/time/toxicity-based algorithm, 7, 7 and 4 patients received 1, 2 and 3 fractions of 8 Gy to the tumor, respectively. Nivolumab anti-PD-1 immunotherapy was administered concurrently with RT and continued for 24 cycles, or until disease progression or manifestation of immune-related adverse events (irAEs). Results Early and late RT toxicities were minimal. Three patients developed irAEs (16%). After the 12th cycle, 7/17 (41.2%) and 5/17 (29.4%) patients with HNSCC showed complete (CR) and partial response (PR), respectively. CR was also achieved in the melanoma patient. The objective response rates in HNSCC patients were 57%, 86% and 66%, after 1, 2 and 3 fractions, respectively (overall response rate 70.6%). Most responders experienced an increase in peripheral lymphocyte counts. The median time to progression was 10 months. The 3-year projected locoregional progression-free survival was 35%, while the 3-year disease-specific overall survival was 50%. Conclusions Anti-PD1 uhypo-IRT is safe and effective in patients with recurrent HNSCC. The high objective response rates and the long survival without evidence of disease support further trials on uhypo-IRT.

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The molecular basis of immuno-radiotherapy

Cited by 6 publications

References 194 publications

Exploiting RIG-I-like receptor pathway for cancer immunotherapy

Exploiting RIG-I-like receptor pathway for cancer immunotherapy

Immune Response and Immune Checkpoint Molecules in Patients with Rectal Cancer Undergoing Neoadjuvant Chemoradiotherapy: A Review

Anti-PD-1 immunotherapy with dose-adjusted ultra-hypofractionated re-irradiation in patients with locoregionally recurrent head and neck cancer

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