IGL CDR3 Hydropathy and Antigen Chemical Complementarity Associated with Greater Disease-Free Survival in Lung Adenocarcinoma: Implications for Gender Disparities.

With lung cancer remaining a challenging disease, new approaches to biomarker discovery and therapy development are needed. Recent immunogenomics, adaptive immune receptor approaches have indicated that it is very likely that B cells play an important role in mediating better overall outcomes. As such, we assessed physicochemical features of lung adenocarcinoma resident IGL complementarity determining region-3 (CDR3) amino acid (AA) sequences and determined that hydrophobic CDR3 AA sequences were associated with a better disease-free survival (DFS) probability.

Chemical Complementarity of Breast Cancer Resident, T-Cell Receptor CDR3 Domains and the Cancer Antigen, ARMC3, is Associated With Higher Levels of Survival and Granzyme Expression.

Introduction: One of the most pressing goals for cancer immunotherapy at this time is the identification of actionable antigens.

Methods: This study relies on the following considerations and approaches to identify potential breast cancer antigens: (i) the significant role of the adaptive immune receptor, complementarity determining region-3 (CDR3) in antigen binding, and the existence cancer testis antigens (CTAs); (ii) chemical attractiveness; and (iii) informing the relevance of the integration of items (i) and (ii) with patient outcome and tumor gene expression data.

Results: We have assessed CTAs for associations with survival, based on their chemical complementarity with tumor resident T-cell receptor (TCR), CDR3s.

A Bioinformatics Assessment Indicating Better Outcomes With Breast Cancer Resident, Immunoglobulin CDR3-MMP2 Binding.

Background/aim: The recombination of V, D, and J immunoglobulin (IG) gene segments leads to many variations in the amino acids (AAs) encoded at that site, the complementarity determining region-3 (CDR3). Thus, cancer patients may have varying degrees of CDR3 AA binding specificity for cancer proteases, for example, matrix metalloproteinase 2 (MMP2). MMP2 in breast cancer has been found to contribute to metastasis and is used as a marker for tumor staging.

Tumor resident, TRA anti-viral CDR3 chemical sequence motifs are associated with a better breast cancer outcome.

While for certain cancers, such as cervical cancer, the link to viral infections is very strong and very clear, other cancers represent a history of links to viral infections that are either co-morbidities or drive the cancer in ways that are not yet fully understood, for example the "hit and run" possibility. To further understand the connection of viral infections and the progress of breast cancer, we identified the chemical features of known anti-viral, T-cell receptor alpha chain (TRA) complementarity determining region-3 (CDR3) amino acid sequences among the CDR3s of breast cancer patient TRA recombinations and assessed the association of those features with patient outcomes. The application of this novel paradigm indicated consistent associations of tumor-derived, anti-CMV CDR3 chemical sequence motifs with better breast cancer patient outcomes but did not indicate an opportunity to establish risk stratifications for other cancer types.

TCR CDR3-antigen chemical complementarity associated with poor ovarian cancer outcomes: A vestigial immune response to early cancer antigens?

Ovarian cancer continues to present significant challenges for early detection and treatment, indicating a need for novel approaches to improve disease outcomes. In this report, we applied a previously described algorithm for detecting chemical complementarity between candidate cancer antigens and complementarity determining region-3 (CDR3) amino acid sequences from tumor resident T-cell receptors. Current literature indicates an association between high CDR3-cancer antigen complementarity and improved survival outcomes.

Chemical complementarity between tumor resident, T-cell receptor CDR3s and MAGEA3/6 correlates with increased melanoma survival: Potential relevance to MAGE vaccine auto-reactivity.

Cancer testis antigens have been of interest as possible targets for cancer immunotherapies. To better understand the opportunities for the use of such immunotherapy targets, we used a chemical complementarity scoring algorithm and an original web tool to establish aspects of electrostatic complementarity of the CTAs, MAGEA3 and MAGEA6, with melanoma specimen resident, T-cell receptor (TCR) complementarity determining region 3 (CDR3) amino acid sequences. Greater electrostatic complementarity between T-cell receptor CDR3 and tumor CTAs MAGEA3/6 was associated with a greater probability of overall survival, for both the cancer genome atlas and Moffitt Cancer Center samples; and was associated with high levels of T-cell cytotoxicity-related gene expression.

Tumor Resident, B-Cell Receptor Chemical Characteristics Associated with Better Overall Survival for Neuroblastoma.

Pediatric neuroblastoma (NBL) is one of the most common pediatric cancers, and it can often be aggressive. Genetic and demographic factors can correlate with the severity of NBL, but the variations in the B-cell receptors (BCRs) or immunoglobulin proteins present in the NBL tumors, and their relationships to survival, are not well understood. BCRs contain variations in their complementary determining region-3 (CDR3s) amino acid sequences, due to variable recombinations of the V- and J-gene segments.

Chemical complementarity between immune receptor CDR3s and candidate cancer antigens correlating with reduced survival: evidence for outcome mitigation with corticosteroid treatments.

The evaluation of physicochemical characteristics of extensive adaptive immune receptor (IR) recombination sequence collections has led to the discovery of many correlations of those sequences and a variety of diseases, including cancer. In the cancer setting, these evaluations have recently focused on the adaptive IR, complementarity determining region-3 (CDR3) amino acid (AA) sequences, which play a major role in antigen binding. For example, the chemical complementarities of the tumor resident, CDR3 AA sequences and the BRAFV600E mutant, common in melanoma, have proved informative with regard to outcomes.

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

It became apparent several years ago that RNAseq and exome files prepared from tissue could be mined for adaptive immune receptor (IR) recombinations, which has given extra value to datasets originally intended for gene expression or mutation studies. For example, recovery of IR recombination reads from tumour specimen genomics files can correlate with survival rates. In particular, many benchmarking processes have been applied to the two sets of the IR recombination reads obtained from the cancer genome atlas files, but these two sets have never been directly compared.

Electrostatic Complementarity of T-Cell Receptor-Alpha CDR3 Domains and Mutant Amino Acids Is Associated with Better Survival Rates for Sarcomas.

While sarcoma immunology has advanced with regard to basic, and even some applied topics, this disease has not been subject to more recent immunogenomics approaches. Thus, we assessed the immune receptor recombinations available from the cancer genome atlas (TCGA) sarcoma database via tumor sample exome and RNASeq files. Results indicated that recovery of T-cell receptor-alpha recombination reads (TRA) correlated with a better survival rate, with the expression of T-cell biomarkers, and with tumor sample apoptosis signatures consistent with the longer patient survival times.

Chemical complementarity between immune receptor CDR3s and IDH1 mutants correlates with increased survival for lower grade glioma.

Focusing on highly specific aspects of the immune response is likely to answer a number of basic questions, and in some cases even resolve basic contradictions, in cancer immunology. For example, there are many cases, where chronic inflammation is associated with cancer development, and many other cases where an immune response represents an anticancer process. In this study, using bioinformatics algorithms, we examined the chemical relationships between the amino acid sequences of the complementarity-determining region-3 (CDR3) represented by immune receptors associated with lower grade glioma and isocitrate dehydrogenase-1 (IDH1) mutants.