Rosner, S. | Search bioRxiv

bioRxiv2023

Consistent decrease in conifer embolism resistance from the stem apex to base resulting from axial trends in tracheid and pit traits

Drought-induced embolism formation in conifers is associated with several tracheid and pit traits, which vary in parallel from stem apex to base. We tested whether this axial anatomical variability is associated with a progressive variation in embolism vulnerability along the stem from apex to base. We assessed the xylem pressure at 50% loss of conductivity (P50), the tracheid hydraulic diameter (Dh) and mean pit membrane area (PMA) on longitudinal stem segments extracted at different distances from the stem apex (DFA) in a Picea abies and an Abies alba tree. In both trees, Dh and PMA scaled with DFA0.2. P50 varied for more than 3 MPa from the treetop to the stem base, according to a scaling of -P50 with DFA-0.2. The largest Dh, PMA and P50 variation occurred for DFA<1.5 m. PMA and Dh scaled isometrically (exponent b=1). Pit traits vary proportionally with tracheid lumen diameter. Apex-to-base trends in tracheid and pit traits determine a large DFA-dependent P50 variability. Such a DFA effect on P50 did not receive sufficient attention so far, although analysing the relationships P50 vs. DFA is fundamental for the assessment of embolism vulnerability at the individual level. HighlightsO_LIConifer embolism vulnerability depends on pit properties, in agreement with published data. C_LIO_LIPit dimensions increase with tracheid lumen diameter, in agreement with published data C_LIO_LITracheid lumen diameter and pit dimensions increase progressively from the stem apex to base, in agreement with published data. C_LIO_LIXylem vulnerability to embolism formation (P50) varies for > 3 MPa from the stem apex to base, with the largest variation occurring within 1.5 m from the stem apex. C_LIO_LIAxial anatomical patterns should be accounted for when analyzing hydraulic properties at individual, intra- and inter-specific scales. C_LI

plant biology↗

bioRxiv2023

Elucidating the heterogeneity of immunotherapy response and immune-related toxicities by longitudinal ctDNA and immune cell compartment tracking in lung cancer

PurposeAlthough immunotherapy is the mainstay of therapy for advanced non-small cell lung cancer (NSCLC), robust biomarkers of clinical response are lacking. The heterogeneity of clinical responses together with the limited value of radiographic response assessments to timely and accurately predict therapeutic effect -especially in the setting of stable disease-call for the development of molecularly-informed real-time minimally invasive predictive biomarkers. In addition to capturing tumor regression, liquid biopsies may be informative in evaluating immune-related adverse events (irAEs). Experimental designWe investigated longitudinal changes in circulating tumor DNA (ctDNA) in patients with metastatic NSCLC who received immunotherapy-based regimens. Using ctDNA targeted error-correction sequencing together with matched sequencing of white blood cells and tumor tissue, we tracked serial changes in cell-free tumor load (cfTL) and determined molecular response for each patient. Peripheral T-cell repertoire dynamics were serially assessed and evaluated together with plasma protein expression profiles. ResultsMolecular response, defined as complete clearance of cfTL, was significantly associated with progression-free (log-rank p=0.0003) and overall survival (log-rank p=0.01) and was particularly informative in capturing differential survival outcomes among patients with radiographically stable disease. For patients who developed irAEs, peripheral blood T-cell repertoire reshaping, assessed by significant TCR clonotypic expansions and regressions were noted on-treatment. ConclusionsMolecular responses assist with interpretation of heterogeneous clinical responses especially for patients with stable disease. Our complementary assessment of the tumor and immune compartments by liquid biopsies provides an approach for monitoring of clinical benefit and immune-related toxicities for patients with NSCLC receiving immunotherapy. Statement of translational relevanceLongitudinal dynamic changes in cell-free tumor load and reshaping of the peripheral T-cell repertoire capture clinical outcomes and immune-related toxicities during immunotherapy for patients with non-small cell lung cancer.

genomics↗