The methods disclosed herein relate to an improved tool incorporating platelet count into a multi-biomarker based outcome risk stratification model for evaluating mortality risk in pediatric patients having sepsis. The methods described here are useful for treating sepsis, for point of care clinical decision support, for stratifying septic shock patients based on baseline mortality risk, and for clinical trial design, among other uses.

The disclosure relates to compounds of formula (A) and formula (I), e.g.:

##STR00001##

or a pharmaceutically acceptable salt thereof, wherein R.sup.1, R.sup.2, R.sup.3, R.sup.4, L.sup.1, L.sup.2, L.sup.3, Y, and Q are as described herein. Compounds of formula (A) and formula (I) and pharmaceutical compositions thereof are inhibitors of at least one or more of ?.sub.V?.sub.8, ?.sub.V?.sub.1, and ?.sub.V?.sub.6 integrins. Also disclosed are methods for treating fibrosis such as nonalcoholic steatohepatitis (NASH), idiopathic pulmonary fibrosis (IPF) and nonspecific interstitial pneumonia (NSIP), and cancer comprising administration of the compounds and pharmaceutical compositions thereof.

The present disclosure provides granzyme-activatable and detectable membrane-interacting peptides that, following activation, can interact with phospholipid bilayers, such as cell membranes. The present disclosure also provides methods of use of such peptides, as well as compositions comprising such peptides. The peptides of the present disclosure are of the general structure X.sup.1a-A-X.sup.2ZX.sup.1b, where A is a membrane-interacting peptide region having a plurality of nonpolar hydrophobic amino acid residues that, following separation from portions Z, is capable of interaction with a phospholipid bilayer; Z is an inhibitory peptide region that can inhibit the activity of portion A; X.sup.2 is a granzyme-cleavable linker that can be cleaved to release cleavage products from the compound; and X.sup.1a and X.sup.1b are optionally-present chemical handles that facilitate conjugation of various cargo moieties to the compound.

Described herein are methods for identifying immune cell-specific antigens and compositions for use in the methods.

The disclosure provides methods of determining patient populations amenable or suitable for immunomodulatory treatment of disease such as cancer by measuring the relative or absolute levels of T-cell sub-populations correlated with disease such as cancer.

The present invention relates to a method of predicting, assessing or monitoring the sensitivity of a subject having a cancer to an immunotherapy, preferably to an immunotherapy combining at least two immunotherapeutic agents, and to corresponding kits and uses thereof. The method of predicting, assessing or monitoring the sensitivity of a subject having a tumor to an immunotherapy typically comprises a step of assessing, before any immunotherapeutic treatment step in the subject, the presence of CD4+CD25highCD39high T cells in a tumor sample of the subject, the presence of CD4+CD25highCD39high T cells in the tumor sample of the subject being indicative of sensitivity of the subject to the immunotherapy, and the absence of CD4+CD25highCD39high T cells in the tumor sample of the subject being indicative of resistance of the subject to the immunotherapy.

The present invention relates to a method of predicting assessing or monitoring the sensitivity of a subject having a cancer to a combination therapy, preferably to a therapy combining an immunotherapeutic agent and an anti-angiogenic agent, and to corresponding kits and uses thereof. The method of predicting, assessing or monitoring the sensitivity of a subject having a cancer or malignant tumor to a proposed combination therapy typically comprises a step a) of determining, in a biological sample from said subject, the presence, absence or expression level or proportion of at least one biomarker, for example at least two biomarkers, and when the expression level or proportion is determined a step b) of comparing said expression level or proportion to reference expression level(s) or to reference expression ratio(s), thereby predicting, assessing or monitoring whether the subject having a tumor is responsive or resistant to the proposed combination therapy.

. There is great interest in developing strategies to identify proteolytic substrates. Synthetic peptide libraries are among the most widely used to screen substrates-based activity, however, this technique is limited by the size of libraries and is time-consuming. Several combinatorial library-based display technologies such as phage, bacteria and yeast display, can identify better substrates for protease activity with higher-throughput sequencing and enrichment of specific substrates over multiple rounds of selection. Even though these profiling techniques provide greater coverage of protease cleavable substrates, such cells are less capable of accessing difficult to deliver sites, pose immunogenicity concerns, and have not been applied to discriminate on-from off-target activity in vivo. Disclosed herein are in vitro and in vivo methods for screening protease substrates.

The disclosure provides methods and compositions to digitally profile biological activity by detecting the activity of at least two biomarkers using protease activity sensors or biocomparators.

Described herein are methods for identifying immune cell-specific antigens and compositions for use in the methods.