The incidence of hepatocellular carcinoma (HCC) is increasing and 40% of patients are diagnosed at advanced stages. Over the past 5 years, the number of clinical available treatments have dramatically increased for HCC, making patient management particularly complex. Immune checkpoint inhibitors (ICIs) have improved the overall survival of patients showing a durable treatment benefit over time, and a different response pattern with respect to tyrosine kinase inhibitors (TKIs). Although improved survival in responder cases, a sizeable group of patients are primary progressors or are ineligible for immunotherapy. Indeed, patients with non-viral etiologies, such non-alcoholic steatohepatitis (NASH), and alterations in specific driver genes might be less responsive to immunotherapy. Therefore, improving the comprehension of mechanisms of drug resistance and identifying biomarkers informative of the best treatment approach are required actions to improve patient survival. Numerous evidence indicated non-coding RNAs (ncRNAs) as pivotal players in cancer. Molecular mechanisms through which ncRNAs exert their effects in cancer progression and drug resistance have been widely investigated. Nevertheless, there are no studies summarizing the synergistic effect between ncRNA-based strategies and TKIs or ICIs in the preclinical setting. This review aims to provide up-to-date information regarding the possible use of ncRNAs as therapeutic targets in association with molecular targeted agents and immunotherapies and as predictive tools for the selection of optimized treatment options in advanced HCCs.

Instead of tissue-based detection, blood-based tumor mutation burden (bTMB) is becoming an alternative promising alternate to predict the response of immune checkpoint inhibitor in cancers, especially non-small-cell lung cancer. Although bTMB is more convenient and less invasive, many evidences identified its limited predictive ability and less accurate discrimination of candidates to receive immunotherapy. Several ways of adjustments have been applied to improve the clinical usefulness of bTMB, such as setting restriction for threshold of allele frequency to exclude some unwanted mutations. But many questions remained to be explored such as the number and the type of mutations that should be incorporated into the bTMB estimation. This viewpoint summarized the current attempts to modify bTMB and provided granular aspects that have implications for further enhancement of bTMB’s predictive capability.

There is currently no effective treatment strategy for the recurrent/metastatic adenoid cystic carcinoma (R/M ACC). Furthermore, recent single-agent and combination immunotherapy trials have failed in unselected ACC cohorts unlike non-ACC salivary gland cancers. Genomic profiling revealed no actionable targets but NOTCH1 and KDM6A frameshift and CTCF splice site mutations (no MYB/L fusion) with a low TMB, MSS and negative PD-L1. We recommended anti-PD-1 plus anti-CTLA-4 combination based on TMB 2-fold greater than median TMB in ACC, tumor harboring multiple immunogenic frameshift or splice site mutations, and PD-L1 negativity. Accordingly, we achieved a complete response in a radiotherapy and chemotherapy-refractory patient with locally recurrent lacrimal gland ACC and lung metastasis following personalized immunotherapy in combination with integrative therapeutics. Therefore, it is crucial to assess not only conventional immune biomarkers but also patient-specific parameters.

Gastric cancer is a heterogeneous group of diseases with only a fraction of patients responds to immunotherapy. The relationships between tumor DNA damage response, the immune system and immunotherapy have recently attracted attention. Accumulating evidence indicate that DNA repair landscape is a significant factor in driving response to immune checkpoint blockade (ICB) therapy. In this study, to explore new prognostic and predictive biomarkers for gastric cancer patients who are sensitive and responsible to immunotherapy, we developed a novel 15-DNA repair gene signature (DRGS) and its related scoring system and evaluated the efficiency of DRGS in discriminating different molecular and immune characteristics and therapeutic outcomes of gastric adenocarcinoma. The results showed that DRGS high score patients showed significantly better therapeutic outcomes compared to DRGS low score patients (P < 0.001). Integrated analysis of multi-omics data demonstrated that the patients with high DRGS score were characteristic of high levels of anti-tumor lymphocytes infiltration, tumor mutation burden (TMB) and PD-L1 expression, and these patients exhibited a longer overall survival and may benefit more from ICB therapy, as compared to the low-score patients. Therefore, the DRGS and its scoring system may have implications in tailoring immunotherapy in gastric cancers.

In times of water scarcity, water conservation measures from authorities are primarily directed to the residential sector—homeowners and renters who engage in individual activities to reduce water consumption. Business owners, manufacturers, and institutional workers—the ICI sector, generally, do not receive targeted information and education on water savings measures, and when they do, the information, typically, refers to indoor technologies, and behavior choice. In answer to this shortfall, this research illustrates how the ICI sector might engage in outdoor water conservation and, thus, realize water savings using the well-established Pittenger’s Simplified Landscape Irrigation Design Estimation (SLIDE) formula that estimates outdoor water conservation/savings for the lesser studied industrial, commercial, and institutional (ICI) sector. We applied the SLIDE formula five diverse climate areas in Texas to demonstrate the potential water savings in each, as well as identifying the type of water technology measures that yielded the greatest water savings for outdoor ICI landscapes. Overall, the greatest water savings for outdoor ICI landscapes was realized through smartscape design with soil moisture sensors-SMS technology, second best. Our findings will provide ICI facility owners/managers with knowledge and examples of a simplified system for quantitative decision making when considering choices among technologies and/or practices toward outdoor water conservation for their own facilities.