Due to the emergence of traditional drug resistance in tumor treatment, the anti-cancer therapies are facing multiple challenges. Immunotherapy, as a new and universal treatment, has been gradually concerned. The macrophages, as an important part of the immune system, play an important role in it. Many studies have shown that immune state is essential in cancer progression and prognosis, rebuilding the architecture and functional orientation of the tumor region. Most tumors are complex ecosystems that change temporally and spatially under the pressure of proliferation, apoptosis, and extension of every cell in the microenvironment. Here, we review how macrophages states can be dynamically altered in different metabolic states and we also focus on the formation of immune exhaustion. Finally, we look forward to the explorations of clinical treatment for immune metabolism process.

Proteomics emerges from the protein identification to protein functional elucidation, which depends to a large extent on the characterization of protein sequences. However, a large part of proteome sequences remains unannotated due to the limitation in proteolytic digestion by golden standard protease trypsin. Herein, we demonstrated that a cyanobacterial protease VAILase could specifically cleave at the short-chain aliphatic amino acids valine, alanine, leucine, isoleucine and threonine with cleavage specificity about 92% in total for proteomic analysis. The unique features of VAILase cleavage facilitate the characterization of most proteins and exhibit high complementarity to trypsin, and 22% of the covered sequences by VAILase are unique. VAILase can greatly improve the coverages of sequences with abundant aliphatic residues that are usually dark regions in conventional proteomic analysis, such as the transmembrane regions within anion exchanger 1 and photosystem II.

SUMMARY Stable transmission of genetic material during cell division requires accurate chromosome segregation. PLK1 dynamics at kinetochores control establishment of correct kinetochore-microtubule attachments and subsequent silencing of the spindle checkpoint. However, the regulatory mechanism responsible for PLK1 activity in prometaphase has not yet been affirmatively identified. Here we identify Apolo1, which tunes PLK1 activity for accurate kinetochore-microtubule attachments. Apolo1 localizes to kinetochores during early mitosis, and suppression of Apolo1 results in misaligned chromosomes. Using the fluorescence resonance energy transfer (FRET)-based PLK1 activity reporter, we found that Apolo1 sustains PLK1 kinase activity at kinetochores for accurate attachment during prometaphase. Apolo1 is a cognate substrate of PLK1, and the phosphorylation enables PP1γ to inactivate PLK1 by dephosphorylation. Mechanistically, Apolo1 constitutes a bridge between kinase and phosphatase, which governs PLK1 activity in prometaphase. These findings define a previously uncharacterized feedback loop by which Apolo1 provides fine-tuning for PLK1 to guide chromosome segregation in mitosis.