Combined α-programmed death-1 monoclonal antibody blockade and fractionated radiation therapy reduces tumor growth in mouse EL4 lymphoma

Abstract

The programmed death (PD) pathway is frequently present in the tumor microenvironment (TME) and suppresses tumor immunity by inhibiting the activity of tumor-infiltrating lymphocytes (TILs), particularly, CD8 + lymphocytes. PD immunotherapy involves stimulation of the immune response in the region surrounding the tumor but is insufficient to prevent tumor progression. Therefore, in this study, we examined the effects of combined PD immunotherapy with fractionated radiotherapy (RT) on antitumor immunity and tumor growth in lymphoma. The immune cell profiles of the TME, blood, and secondary lymphoid organs were determined 7 days after treatment. Four combination therapies were compared. The synergistic effects of αPD-1 mAb and fractionated RT on increased CD8 + lymphocytes in the TME, blood, and secondary lymphoid organs led to substantial tumor regression in mouse EL4 lymphoma, both locally and systemically. Fractionated RT for 4 days followed by αPD-1 mAb therapy was significantly superior to other schemes in terms of overall survival rates and curative rates in xenograft model mice. Our data indicated that substantial immune responses occurred following combination therapy with fractionated RT and αPD-1 mAb immunotherapy. Our findings provide important insights into the use of RT plus αPD-1 mAb as an efficacious combinatorial therapy.

Carrier-Free Nanovaccine: An Innovative Strategy for Ultrahigh Melanoma Neoantigen Loading

“…Reports have shown that a stronger antigen-specific T-cell-mediated immune response typically occurs on the second exposure to the same antigen. , Therefore, to determine the specific killing effect of nanovaccines on tumor cells, we collected splenocytes from immunized mice and used them in a coculture as effector T cells (E) to assess the response of CD8 + T-cell subpopulations of splenocytes to target cells B16F10 (T). , Compared to the blank, the number of splenocytes in the Obsl1, CpG + Obsl1, and 2′F-CpG/Obsl1 nanovaccine groups that showed dosage-dependent CD8 + T-cell activity against target cells significantly increased when the E/T ratios were 10:1, 20:1, and 40:1, as shown in Figure l. Furthermore, the nanovaccine group exhibited higher cytotoxicity than the blank, Obsl1, and CpG + Obsl1 groups.…”

Real‐World Efficacy and Safety of Sintilimab‐Based Regimens against Advanced Esophageal Cancer: A Single‐Center Retrospective Observational Study

“…Several preclinical studies have demonstrated that radiotherapy combined with immunotherapy has three major benefits: (1) radiotherapy can regulate the tumor microenvironment and increase the infiltration of cytotoxic T lymphocytes, thereby enhancing the effect of tumor regression and achieving better local control; (2) produce effector and memory immune cells to maintain antitumor immunity, thereby avoiding tumor recurrence and prolonging local control time; and (3) induce “distant effect” and reduce the risk of distant metastasis [ 27 – 29 ]. In a phase 2 trial in Korea, 28 patients with stage Ib-III ESCC received chemoradiotherapy along with pembrolizumab, followed by surgery and postoperative pembrolizumab maintenance therapy.…”

Positron emission tomography molecular imaging to monitor anti-tumor systemic response for immune checkpoint inhibitor therapy

“…T cell activity through ICI therapy represents an important breakthrough in treating human cancer. ICI treatment alters the TME, the systemic immune microenvironment, and the immune cell composition, thereby resulting in tumor inhibition [10,42]. Unfortunately, only a small fraction of patients treated with ICI are responsive [43,44].…”