An anti-cancer surveillance by the interplay between interferon-beta and retinoblastoma protein RB1

Abstract

Interferon-beta (IFN-β), an extracellular cytokine that initiates signaling pathways for gene regulation, has been demonstrated to function as a tumor suppressor protein through lentiviral gene transduction. In this article, I review the relevant previous works and propose a cell cycle-based, tumor suppressor protein-mediated mechanism of anti-cancer surveillance. IFN-β induces a tumor cell cycle alteration that leads to S phase accumulation, senescence entry, and a loss of tumorigenicity in solid tumor cells. IFN-β does not show a significant cell cycle effect in their normal counterparts. Retinoblastoma protein RB1, another tumor suppressor protein, tightly controls the cell cycle and differentiation of normal cells, preventing them from being significantly impacted by the IFN-β effect. The interplay between IFN-β and RB1 acts as a mechanism of cell cycle-based, tumor suppressor protein-mediated anti-cancer surveillance that can selectively suppress solid tumor or proliferating transformed cells from the loss of control leading to cancer. This mechanism has important implications for the treatment of solid tumors.

Sequential Therapy with Ropeginterferon Alfa-2b and Anti-Programmed Cell Death 1 Antibody for Inhibiting the Recurrence of Hepatitis B-Related Hepatocellular Carcinoma: From Animal Modeling to Phase I Clinical Results

“…The anti-proliferative effects include cell cycle inhibition and apoptosis [ 49 , 50 , 51 ]. In solid tumor cells, they can slow S-phase progression by activating an intra-S phase checkpoint and inducing senescence entry accompanied by a loss of tumorigenicity [ 52 ]. In addition, they stimulate the immune system to elicit anti-tumor activities, including the induction of natural killer cell-dependent and CD8+ T cell-mediated anti-tumor responses [ 53 , 54 ].…”

“…Group 7: Ten HBV-carrying CBA/CaJ mice were s.c. injected with 800 IU/g of rmIFNα (Q2D × 22, days 0-42) and then i.p. injected with 32 µg/g of the anti-PD1 antibody (Q2D × 6, days [44][45][46][47][48][49][50][51][52][53][54].…”