Regulatory T cells (Tregs) characterized by the expression of the master transcription factor forkhead box protein p3 (Foxp3) suppress anticancer immunity, thereby hindering protective immunosurveillance of tumours and hampering effective antitumour immune responses in tumour-bearing hosts, constitute a current research hotspot in the field. However, Tregs are also essential for the maintenance of the immune tolerance of the body and share many molecular signalling pathways with conventional T cells, including cytotoxic T cells, the primary mediators of tumour immunity. Hence, the inability to specifically target and neutralize Tregs in the tumour microenvironment without globally compromising self-tolerance poses a significant challenge. Here, we review recent advances in characterizing tumour-infiltrating Tregs with a focus on the functional roles of costimulatory and inhibitory receptors in Tregs, evaluate their potential as clinical targets, and systematically summarize their roles in potential treatment strategies. Also, we propose modalities to integrate our increasing knowledge on Tregs phenotype and function for the rational design of checkpoint inhibitor-based combination therapies. Finally, we propose possible treatment strategies that can be used to develop Treg-targeted therapies.

Macrophages are the most important phagocytes in vivo. However, the tumor microenvironment can affect the function and polarization of macrophages and form tumor-associated macrophages (TAMs). Usually, the abundance of TAMs in tumors is closely associated with poor prognosis. Preclinical studies have identified important pathways regulating the infiltration and polarization of TAMs during tumor progression. Furthermore, potential therapeutic strategies targeting TAMs in tumors have been studied, including inhibition of macrophage recruitment to tumors, functional repolarization of TAMs toward an antitumor phenotype, and other therapeutic strategies that elicit macrophage-mediated extracellular phagocytosis and intracellular destruction of cancer cells. Therefore, with the increasing impact of tumor immunotherapy, new antitumor strategies to target TAMs are now being discussed.

DNA double-strand breaks (DSBs) are highly toxic lesions that can impair cellular homeostasis and genome stability to result in tumorigenesis for inappropriate repair. Although DSBs are repaired by homologous recombination (HR) or non-homologous end-joining (NHEJ), the related mechanisms are still incompletely unclear. Indeed, more and more evidences indicate that the methylation of histone lysine has an important role in choosing the pathways of DNA repair. For example, tri-methylated H3K36 is required for HR repair, while di-methylated H4K20 can recruit 53BP1 for NHEJ repair. Here, we reviewed the recent progress in the molecular mechanisms by which histone methylation functions in DNA double-strand breaks repair (DSBR). The insight into the mechanisms of histone methylation repairing DNA damage will supply important cues for clinical cancer treatment.

BackgroundFor the recurrence of head and neck cancer after operation and radiotherapy, the local control of radioactive seed implantation is good, and it has a certain palliative effect. This study aims to investigate the acute and late side effects of a three-dimentional printing non co-planar template (3D–PNCT) for computed tomography (CT)-guided radioactive 125I seed (RIS) implantation in recurrent cancer of the head and neck.MethodsBetween January 2016 and December 2016, forty-two patients with local recurrent malignant tumors of the head and neck received 3D–PNCT-assisted RIS implantation. The prescribed dose was 110–160 Gy. Preoperative planning design, production of individual guide plates, RIS implantation, postoperative dose evaluation, and follow-up were completed for all patients. Side effects in the skin, mucous membranes, blood and spinal cord were evaluated.ResultsAll patients underwent surgery successfully. Duration of follow-up was 4–14 (median, of 8.5) months. The activity of a single RIS was 0.34–0.7 (median, 0.6) mCi. The number of RIS was 10–126 (median, 34). The number of implantation needles was 4–31 (median, 11). The mean D2cc (dose to the most exposed 2-cc volume) and D0.1cc (dose to the most exposed 0.1-cc volume) of the skin were 24.9 (7.1–85.5) and 47.5 (9.4–167.2), respectively, whereas those of the spinal cord were 8.4 (4.5–33.3) and 14.2 (13.6–63.0), mucosa were 35.1 (4.2–82.8) and 87.0 (6.6–214.1), parotid glands were 16.2 (12.8–19.7) and 29.8 (26.1–33.4) and those of the trachea were 17.9 (2.5–45.9) and 32.7 (3.9–83.9), respectively. No case had an acute reaction of grade ≥ 3. Three cases had a grade-1 skin reaction. Blood toxicity did not occur, nor spinal-cord injury. Xerostomia was not aggravated than that of before brachytherapy. One case had a grade-3 nerve response.Conclusions3D–PNCT-assisted RIS implantation can provide good accuracy for positioning. For local recurrent malignant tumor of head and neck, there were no obvious adverse reactions.

Radioactive iodine-125 (I-125) is the most widely used radioactive sealed source for interstitial permanent brachytherapy (BT). BT has the exceptional ability to deliver extremely high doses that external beam radiotherapy (EBRT) could never achieve within treated lesions, with the added benefit that doses drop off rapidly outside the target lesion by minimizing the exposure of uninvolved surrounding normal tissue. Spurred by multiple biological and technological advances, BT application has experienced substantial alteration over the past few decades. The procedure of I-125 radioactive seed implantation evolved from ultrasound guidance to computed tomography guidance. Compellingly, the creative introduction of 3D-printed individual templates, BT treatment planning systems, and artificial intelligence navigator systems remarkably increased the accuracy of I-125 BT and individualized I-125 ablative radiotherapy. Of note, utilizing I-125 to treat carcinoma in hollow cavity organs was enabled by the utility of self-expandable metal stents (SEMSs). Initially, I-125 BT was only used in the treatment of rare tumors. However, an increasing number of clinical trials upheld the efficacy and safety of I-125 BT in almost all tumors. Therefore, this study aims to summarize the recent advances of I-125 BT in cancer therapy, which cover experimental research to clinical investigations, including the development of novel techniques. This review also raises unanswered questions that may prompt future clinical trials and experimental work.