Chemical complementarity between immune receptors and cancer mutants, independent of antigen presentation protein binding, is associated with increased survival rates

Abstract

Highlights Establishment of an immunological distinction between endometrioid and serous uterine cancers. High priority CDR3s, mutant amino acids (AA) for endometrioid cancer prognosis, therapy tools. Further understanding of CDR3-mutant AA complementarity scoring factors, such as HLA binding.

Exploiting adaptive immune receptor recombination read recoveries from exome files to identify subsets of ALL and to establish TCR features that correlate with better outcomes

“…The physicochemical characteristics of each translated complementarity determining region‐3 (CDR3) sequence for each recovered adaptive IR recombination read were assessed using methods derived from Pappu and colleagues and modified in previous projects 17–25 . (See Table S3 for all physicochemical characterizations of all CDR3s assessed in this report).…”

“…The physicochemical characteristics of each translated complementarity determining region-3 (CDR3) sequence for each recovered adaptive IR recombination read were assessed using methods derived from Pappu and colleagues and modified in previous projects. [17][18][19][20][21][22][23][24][25] (See Table S3 for all physicochemical characterizations of all CDR3s assessed in this report). Microsoft Excel pivot tables were used to obtain the mean physicochemical characteristic of the adaptive IR, CDR3 amino acid (AA) sequence collection recovered from a given, individual tumour bone marrow sample representing a case ID.…”

A comparison of immune receptor recombination databases sourced from tumour exome or RNAseq files: Verifications of immunological distinctions between primary and metastatic melanoma

“…We removed unproductive (out of frame and stop codon) CDR3s and duplications in both cases. We then determined the percentage of the exact CDR3 AA sequence Chobrutskiy et al, 2019;Hsiang et al, 2021;Ostmeyer et al, 2019;Ostmeyer et al, 2020;Yeagley et al, 2021). This approach was applied to the CDR3s recovered from the SKCM WXS and RNAseq files, for four different chemical parameters (Figure 5).…”

“…Likewise, the opportunity to have cost-effective indications regarding tumour immune status, from genomics files prepared to obtain mutations, could be very important in general but especially in locales where cost limits opportunities for stratifying patients. For example, the knowledge that a chemically complementary, immune receptor, complementarity determining region-3 (CDR3)-mutant amino acid (AA) combination, known to represent a good response to the mutant amino acid (Arturo et al, 2020;Hsiang et al, 2021;Yeagley et al, 2021), may indicate rapid immune checkpoint blockade treatment, without further testing; while lack of such combinations could either favour other therapies or justify the costs of additional tests assessing immune status before making a final, immune checkpoint blockade decision.…”

Immune receptor CDR3 chemical features that preserve sequence information are highly efficient in reflecting survival distinctions: A pan‑cancer analysis

“…This approach is based on the simple idea that the CDR3 is the most important region of the IR for antigen recognition (11), and that, particularly in a big data setting, a dominant physicochemical feature could represent a minimum for successful antigen binding and immune mediated reductions in tumor cell numbers (12). From the outset, algorithms were developed to exploit the physicochemical features, and their correlations with data represented by other platforms, such as survival and immune biomarker expression, to identify possible antigen partners (9,(12)(13)(14)(15)(16). For example, single value, physicochemical assessments of tumor resident…”