Kagoshima University

Immune checkpoint blockade (ICB) has significantly improved the survival for many patients with advanced malignancy. However, fewer than 50% of patients benefit from ICB, highlighting the need for more effective immunotherapy options. High-dose interleukin-2 (HD IL-2) immunotherapy, which is approved for patients with metastatic melanoma and renal cell carcinoma, stimulates CD8⁺ T cells and NK cells and can generate durable responses in a subset of patients. Moreover, HD IL-2 may have potential efficacy in patients whose disease has progressed following ICB and plays a vital role in expanding tumor-infiltrating lymphocyte (TIL) in TIL therapy. Despite its potential, the use of HD IL-2 is limited by severe toxicities such as hypotension and vascular leak syndrome. Additionally, only a few patients achieve a good outcome after HD IL-2 therapy. To address these challenges, numerous next-generation IL-2 receptor (IL-2 R) agonists have been developed to exhibit treatment effects while minimizing adverse events. This review will explore IL-2 biology, the clinical application of HD IL-2 therapy, and the development of novel IL-2 R agonists for cancer immunotherapy.

The Common Terminology Criteria for Adverse Events (CTCAE) was originally used to evaluate surgical complications in clinical trials. However, there were some drawbacks, as CTCAE only evaluated the safety of chemotherapy and radiotherapy. The Japan Clinical Oncology Group Postoperative Complication (JCOG PC) criteria was established in 2016. It was based on Clavien-Dindo classification and standardized adverse events (AE) terms and grading definitions of surgical complications. Although the JCOG PC criteria is now widely adopted in clinical practice, validity of the JCOG PC has not yet been examined. This study aimed to validate the JCOG PC criteria against the CTCAE.

We analyzed data from JCOG clinical trials, which included surgery as part of the protocol treatment, and whose postoperative complications were evaluated using the CTCAE and the JCOG PC criteria. We assessed the grade agreement of these two criteria for each postoperative complication. If the point estimate of the proportion of agreement for an AE term was 90 % or higher, CTCAE and JCOG PC criteria grades were considered "equivalent."

We assessed data from 3006 patients across 6 JCOG clinical trials, including 42 early and 25 late postoperative complications. The median proportion of agreement (range) between the CTCAE and JCOG PC criteria was 99.5 % (97.2-100) in early and 99.4 % (89.3-100) in late complications. The point estimations of the proportion of agreement of all early and late postoperative complication items were 90 % or higher.

The JCOG PC criteria was valid for evaluation of postoperative complications.

Attachment site recognition for infecting a definite host is crucial for obligate ectoparasites.Caligus fugu, a marine copepod parasite primarily found on pufferfishes, has a unique host-/organ-specificity.The infective stage of the species exclusively infects host fins as the attachment site.However, so far, little is known about the mechanism underlying the specificity of C. fugu.In this study, transcriptomic profiles of the infective first copepodid stage (CI) along with the pre- and a post-infective stage, i.e., second nauplii (NII) and second copepodids (CII), resp., were investigated.The de novo assembled transcriptome of C. fugu showed that a high number of transcripts showed high homol. to those of relative species, Caligus rogercresseyi (94.7 %) and Lepeophtheirus salmonis (91.0 %), suggesting that only a small portion of species-specific genes contribute to interspecific differences, such as host-seeking.Importantly, no gene was noted from the odorant receptors and gustatory receptors families in C. fugu transcripts, similar to L. salmonis genome.Genes related to chemosensing such as the ionotropic glutamate receptors (iGluR) or ionotropic receptors (IRs), viz., GRIA2, GRIA3, GRID2, GRIK2, GRIK3, IR21a, IR25a, IR40a, and IR93a, likely involved in host-seeking, were highly expressed during CI among the three stages.In addition, inositol 1,4,5-triphosphate receptor-associated 2, another potential candidate gene involved in host-seeking, was significantly upregulated in CI compared with that in NII and maintained at the same level in CII.Our present transcriptomic data should offer a foundation for further investigations on various biol. aspects, such as the host-/organ-specificity of sea lice.