Tumor immune escape is an important strategy of tumor survival. There are many mechanisms of tumor immune escape, including immunosuppression, which has become a research hotspot in recent years. The programmed death ligand-1/programmed death-1 (PD-L1/PD-1) signaling pathway is an important component of tumor immunosuppression, which can inhibit the activation of T lymphocytes and enhance the immune tolerance of tumor cells, thereby achieving tumor immune escape. Therefore, targeting the PD-L1/PD-1 pathway is an attractive strategy for cancer treatment; however, the therapeutic effectiveness of PD-L1/PD-1 remains poor. This situation requires gaining a deeper understanding of the complex and varied molecular mechanisms and factors driving the expression and activation of the PD-L1/PD-1 signaling pathway. In this review, we summarize the regulation mechanisms of the PD-L1/PD-1 signaling pathway in the tumor microenvironment and their roles in mediating tumor escape. Overall, the evidence accumulated to date suggests that induction of PD-L1 by inflammatory factors in the tumor microenvironment may be one of the most important factors affecting the therapeutic efficiency of PD-L1/PD-1 blocking.

SUMMARYHigher plants have evolved multiple proteins in the RNase III family to produce and regulate different classes of small RNAs with specialized molecular functions. In rice (Oryza sativa), numerous genomic clusters are targeted by one of two microRNAs (miRNAs), miR2118 and miR2275, to produce secondary small interfering RNAs (siRNAs) of either 21 or 24 nucleotides in a phased manner. The biogenesis requirements or the functions of the phased small RNAs are completely unknown. Here we examine the rice Dicer-Like (DCL) family, including OsDCL1, -3a, -3b and -4. By deep sequencing of small RNAs from different tissues of the wild type and osdcl4-1, we revealed that the processing of 21-nucleotide siRNAs, including trans-acting siRNAs (tasiRNA) and over 1000 phased small RNA loci, was largely dependent on OsDCL4. Surprisingly, the processing of 24-nucleotide phased small RNA requires the DCL3 homolog OsDCL3b rather than OsDCL3a, suggesting functional divergence within DCL3 family. RNA ligase-mediated 5¢ rapid amplification of cDNA ends and parallel analysis of RNA ends (PARE)/degradome analysis confirmed that most of the 21-and 24-nucleotide phased small RNA clusters were initiated from the target sites of miR2118 and miR2275, respectively. Furthermore, the accumulation of the two triggering miRNAs requires OsDCL1 activity. Finally, we show that phased small RNAs are preferentially produced in the male reproductive organs and are likely to be conserved in monocots. Our results revealed significant roles of OsDCL4, OsDCL3b and OsDCL1 in the 21-and 24-nucleotide phased small RNA biogenesis pathway in rice.

The adaptive value of transgenerational effects (the ancestor environmental effects on offspring) in changing environments has received much attention in recent years, but the related empirical evidence remains equivocal. Here, we conducted a meta‐analysis summarising 139 experimental studies in plants and animals with 1170 effect sizes to investigate the generality of transgenerational effects across taxa, traits, and environmental contexts. It was found that transgenerational effects generally enhanced offspring performance in response to both stressful and benign conditions. The strongest effects are in annual plants and invertebrates, whereas vertebrates appear to benefit mostly under benign conditions, and perennial plants show hardly any transgenerational responses at all. These differences among taxonomic/life‐history groups possibly reflect that vertebrates can avoid stressful conditions through their mobility, and longer‐lived plants have alternative strategies. In addition to environmental contexts and taxonomic/life‐history groups, transgenerational effects also varied among traits and developmental stages of ancestors and offspring, but the effects were similarly strong across three generations of offspring. By way of a more comprehensive data set and a different effect size, our results differ from those of a recent meta‐analysis, suggesting that transgenerational effects are widespread, strong and persistent and can substantially impact the responses of plants and animals to changing environments.