Targeting two radiation-induced immunosuppressive pathways to improve the efficacy of normofractionated radiation therapy in a preclinical colorectal cancer model.

Purpose: We have previously demonstrated in a murine colorectal cancer model that normofractionated RT (normoRT: 18 × 2 Gy) induced MDSC infiltration and PD-L1 expression, while hypofractionated RT (hypoRT: 3 × 8 Gy) induced Treg. Here, we wanted to assess whether the association of normoRT with treatments that target two radiation-induced immunosuppressive pathways (MDSC and PD-L1) could improve tumor control.

Materials And Methods: Subcutaneous tumors were induced using colon tumor cells (CT26) in immunocompetent mice (BALB/c) and were treated with RT alone (18 × 2 Gy or 3 × 8 Gy), or concomitantly with 5-Fluorouracil (5FU) (10 mg/kg) to deplete MDSC, and/or anti-PD-L1 (10 mg/kg).

Chemotherapy to potentiate the radiation-induced immune response.

Chemoradiation (CRT) is a conventional therapy used in local cancers, especially when they are locally advanced. Studies have shown that CRT induces strong anti-tumor responses involving several immune effects in pre-clinical models and humans. In this review, we have described the various immune effects involved in CRT efficacy.

Response to Chemoimmunotherapy Is Associated With Expansion of Systemic Antitumor CD4 + Th1 Response in Metastatic Non-Small Cell Lung Cancer.

Limited data have reported the evolution of antitumor immune responses under chemoimmunotherapy (chemo-IO) in patients with metastatic non-small cell lung cancer. In this concise study, we performed dynamic monitoring of antitumor CD4 + T helper 1 (Th1) response in peripheral blood from 12 patients receiving a first-line chemo-IO. Tumor-reactive CD4 + Th1 cells were assessed within blood lymphocytes using interferon-gamma enzyme-linked immunospot assay to detect telomerase (TERT)-specific T cells at baseline, 3 and 12 months after treatment.

Interplay between plasmacytoid dendritic cells and tumor-specific T cells in peripheral blood influences long-term survival in non-small cell lung carcinoma.

Plasmacytoid dendritic cells (pDCs) represent a subset of antigen-presenting cells that play an ambivalent role in cancer immunity. Here, we investigated the clinical significance of circulating pDCs and their interaction with tumor-specific T cell responses in patients with non-small cell lung cancer (NSCLC, n = 126) . The relation between intratumoral pDC signature and immune checkpoint inhibitors efficacy was also evaluated.

TIE-2 Signaling Activation by Angiopoietin 2 On Myeloid-Derived Suppressor Cells Promotes Melanoma-Specific T-cell Inhibition.

Myeloid-derived suppressor cells (MDSCs) are a heterogeneous group of immune suppressive cells detected in several human cancers. In this study, we investigated the features and immune suppressive function of a novel subset of monocytic MDSC overexpressing TIE-2 (TIE-2 M-MDSC), the receptor for the pro-angiogenic factor angiopoietin 2 (ANGPT2). We showed that patients with melanoma exhibited a higher circulating rate of TIE-2 M-MDSCs, especially in advanced stages, as compared to healthy donors.

Anti-PD-1/Anti-PD-L1 Drugs and Radiation Therapy: Combinations and Optimization Strategies.

Immune checkpoint inhibitors have been associated with long-term complete responses leading to improved overall survival in several cancer types. However, these novel immunotherapies are only effective in a small proportion of patients, and therapeutic resistance represents a major limitation in clinical practice. As with chemotherapy, there is substantial evidence that radiation therapy promotes anti-tumor immune responses that can enhance systemic responses to immune checkpoint inhibitors.

Chemoradiation triggers antitumor Th1 and tissue resident memory-polarized immune responses to improve immune checkpoint inhibitors therapy.

Background: Multiple synergistic combination approaches with cancer drugs are developed to overcome primary resistance to immunotherapy; however, the mechanistic rationale to combine chemoradiotherapy (CRT) with immune checkpoint inhibitors remains elusive.

Methods: This study described the immunological landscape of tumor microenvironment (TME) exposed to CRT. Tumor samples from patients with rectal cancer (n=43) treated with neoadjuvant CRT or radiotherapy were analyzed by nanostring and immunohistochemistry.

Cisplatin-based chemoradiation decreases telomerase-specific CD4 TH1 response but increases immune suppressive cells in peripheral blood.

Background: The synergistic effect of chemoradiation (CRT) has been previously demonstrated in several cancer types. Here, we investigated the systemic immune effects of CRT in patients with lung or head and neck cancer.

Materials And Methods: Peripheral blood mononuclear cells were collected at baseline and 1 month after treatment from blood samples of 29 patients treated with cisplatin-based chemoradiotherapy for lung or head and neck cancer.