Background Currently, due to synergy enhancement of anti‐tumor effects and potent stimulation of abscopal effects, combination therapy with irradiation and programmed cell death protein 1/programmed death‐ligand 1 (PD‐1/PD‐L1) immune checkpoint inhibition (immuno‐radiotherapy, iRT) has revolutionized the therapeutic guidelines. It has been demonstrated that tumor‐draining lymph nodes (TDLN) are essential for effective antitumor immunity induced by radiotherapy, immunotherapy, or iRT. Given that the function of TDLN in iRT remains unclear, this study aimed to investigate the function and mechanism of TDLN in iRT‐induced abscopal effects. Methods The function of TDLN was evaluated using unilateral or bilateral MC38 and B16F10 subcutaneous tumor models with or without indicated TDLN. The flow cytometry, multiple immunofluorescence analysis, and NanoString analysis were utilized to detect the composition and function of the immune cells in the primary and abscopal tumor microenvironment. Additionally, we tempted to interrogate the possible mechanisms via RNA‐sequencing of tumor‐infiltrating lymphocytes and TDLN. Results TDLN deficiency impaired the control of tumor growth by monotherapy. Bilateral TDLN removal rather than unilateral TDLN removal substantially curtailed iRT‐stimulated anti‐tumor and abscopal effects. Furthermore, in the absence of TDLN, the infiltration of CD45+ and CD8+ T cells was substantially reduced in both primary and abscopal tumors, and the anti‐tumor function of CD8+ T cells was attenuated as well. Additionally, the polarization of tumor‐associated macrophages in primary and abscopal tumors were found to be dependent on intact bilateral TDLN. RNA‐sequencing data indicated that impaired infiltration and anti‐tumor effects of immune cells partially attributed to the altered secretion of components from the tumor microenvironment. Conclusions TDLN play a critical role in iRT by promoting the infiltration of CD8+ T cells and maintaining the M1/M2 macrophage ratio.

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Proper spindle orientation is essential for cell fate determination and tissue morphogenesis. Recently, accumulating studies have elucidated several factors that regulate spindle orientation, including geometric, internal and external cues. Abnormality in these factors generally leads to defects in the physiological functions of various organs and the development of severe diseases. Herein, we first review models that are commonly used for studying spindle orientation. We then review a conservative heterotrimeric complex critically involved in spindle orientation regulation in different models. Finally, we summarize some cues that affect spindle orientation and explore whether we can establish a model that precisely elucidates the effects of spindle orientation without interfusing other spindle functions. We aim to summarize current models used in spindle orientation studies and discuss whether we can build a model that disturbs spindle orientation alone. This can substantially improve our understanding of how spindle orientation is regulated and provide insights to investigate this complex event.