PD-L2-L

Conclusions Overall, PDL2 expression in TILs could represent as an effective prognostic predictor through its involvement in antitumor immunity within the TNBC tumor microenvironment. These findings further corroborate PDL2 as a potential therapeutic target for TNBC, highlighting the importance of considering immune-related factors in TNBC prognosis and treatment.

These findings suggest that the prognostic impact of PD-L2 expression could be affected by the NLR status.

Integration of the mutation status of 7 genes with FLIPI and performance status is the basis of the clinic-genetic tool, m7- FLIPI, established in patients with advanced stage FL treated with induction rituximab-chemotherapy, predicts for both PFS and OS.8 A 23 gene-expression classifier, like m7-FLIPI, stratifies patients into low and high risk groups, predicting PFS but not OS.9 Interestingly, the validity of these biological-based tools is impacted by the chemotherapy backbone, particularly bendamustine.10 Other biological-based prognostic tools illustrate that certain features of the microenvironment are associated with higher risk of early disease progression following initial therapy including low PDL2 expression as a surrogate for an immune cold microenvironment and lack of intra-follicular CD4 expression.11,12 Imaging Prognostic Markers Baseline positron emission tomography (PET)-based biomarkers such as maximum standardised uptake value (SUVmax) and total metabolic tumour volume (TMTV) are also emerging as predictors of clinical outcomes.13–15 Two retrospective series identified high baseline SUVmax to be associated with inferior clinical outcomes...Predictive Biomarkers There are limited approved predictive biomarkers in FL, with EZH2 mutation status the only validated predictive biomarker to date based on the study showing higher response rates of EZH2- mutated FL patients to the EZH2 inhibitor tazemetostat compared to non-mutated.22 Notably, retrospective studies suggest that baseline EZH2 mutation status or high SUVmax might be linked to differential efficacy of chemotherapy backbones used at induction, providing the tantalizing possibility that a predictive biomarker might inform choice of therapy upfront.13,23,24 Given the growing armamentarium of therapies in the second, third line and beyond space, there is a crying need for predictive biomarkers to guide how we select and sequence therapies for patients...However, we may be at the precipice of change with the emergent biological and imaging-based modalities currently being evaluated alongside clinical studies. In the future, the opportunities where prognostic and/or predictive tools might best serve FL patients include: 1) Using prognostic tools at diagnoses to identify high-risk patients and pairing these patients to highly effective therapies based on predictive biomarkers; 2) Prognostic tools at the interim or end of induction treatment that could guide de-escalation or escalation of therapy and; 3) At relapse junctures, performing a suite of predictive biomarker assessments to allow selection of patients better served by specific therapies.

The combined model showed the best performance. The results of this study suggest that prediction based on the radiomic characteristics of MRI could noninvasively predict the expression of PD-L2 in HCC before surgery and provide a reference for the selection of immune checkpoint blockade therapy.

Our results demonstrate PD-L2 expression in TILs to be significantly associated with better prognosis in TNBCs. Furthermore, our data suggest that PD-L2 could function independently of PD-L1 expression with key regulatory roles in identified immune genes signatures. However, further studies are required to review the prognostic signature of PD-L2 and its role in the tumour microenvironment and immune response.

Moreover, tumor PD-L2 expression was inversely associated with the lymphocytic reaction in advanced stage colon carcinoma, suggesting that PD-L2 may be upregulated by a compensatory mechanism to inhibit T cell-mediated anticancer immunity. Taken together, these results show that tumor PD-L2 expression may be an independent prognostic factor for survival outcome in patients with advanced stage colon carcinoma.