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

Patel, Anishaa R; Patel, Dhruvil; Tu, Yaping N.; Yeagley, Michelle; Chobrutskiy, Andrea; Chobrutskiy, Boris I.; Blanck, George

doi:10.1080/07391102.2022.2070546

Cited by 12 publications

(9 citation statements)

References 26 publications

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“…The chemical complementarity scoring is based on [ 8 ] and was facilitated by the construction of an original web tool, adaptivematch.com [ 5 , 12 , 13 ], which is publicly accessible and has been extensively benchmarked in [ 13 ]. The electrostatic complementarity scores (CSs) are generated by aligning the adaptive IR CDR3 AAs with a candidate antigen peptide sequence.…”

Section: Methodsmentioning

confidence: 99%

“…The above considerations indicate a need for additional immunological parameters for personalized treatments, including ICB treatments and possibly other immunotherapies or even anti-inflammatory therapies [ 5 ]. Specifically, for GBM, cancer testis antigens (CTAs) have come to light as possible targets for immunotherapy [ 6 ], with one very relevant indication that such CTAs can be specifically detected in GBM patients and not in healthy controls [ 7 ].…”

Section: Introductionmentioning

confidence: 99%

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Electrostatic Complementarities of Glioblastoma-Resident T-Cell Receptors and Cancer Testis Antigens Linked to Poor Outcomes and High Levels of Sphingosine Kinase-2 Expression

Arias

Cios

Kacsoh

et al. 2023

Biology

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Introduction. Glioblastoma (GBM) is the most aggressive primary brain tumor in adults. Despite a growing understanding of glioblastoma pathology, the prognosis remains poor. Methods. In this study, we used a previously extensively benchmarked algorithm to retrieve immune receptor (IR) recombination reads from GBM exome files available from the cancer genome atlas. The T-cell receptor complementarity determining region-3 (CDR3) amino acid sequences that represent the IR recombination reads were assessed and used for the generation of chemical complementarity scores (CSs) that represent potential binding interactions with cancer testis antigens (CTAs), which is an approach particularly suited to a big data setting. Results. The electrostatic CSs representing the TRA and TRB CDR3s and the CTAs, SPAG9, GAGE12E, and GAGE12F, indicated that an increased electrostatic CS was associated with worse disease-free survival (DFS). We also assessed the RNA expression of immune marker genes, which indicated that a high-level expression of SPHK2 and CIITA genes also correlated with high CSs and worse DFS. Furthermore, apoptosis-related gene expression was revealed to be lower when the TCR CDR3-CTA electrostatic CSs were high. Conclusion. Adaptive IR recombination reads from exome files have the potential to aid in GBM prognoses and may provide opportunities to detect unproductive immune responses.

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Section: Methodsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Electrostatic Complementarities of Glioblastoma-Resident T-Cell Receptors and Cancer Testis Antigens Linked to Poor Outcomes and High Levels of Sphingosine Kinase-2 Expression

Arias

Cios

Kacsoh

et al. 2023

Biology

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“…The computer code for application of the algorithm is freely available at https://github.com/bchobrut/brca_swcs. In addition, the complementarity scoring, along with a matchup of the CSs and survival data, can be done via the publicly available adaptivematch.com (23)(24)(25), with the web tool having been specifically benchmarked in (25). The Adaptive Match web tool has instructions for use.…”

Section: Ig Cdr3-cancer Protease Peptide Complementarity Scoring Algo...mentioning

confidence: 99%

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

Mandala

Thomson

Gozlan

et al. 2023

Cancer Genomics Proteomics

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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. Thus, this report evaluated the tumor resident, patient specific IG CDR3 binding affinities to cancer proteases to test the hypothesis that greater binding affinities would be associated with a better outcome. Materials and Methods: Using two independent bioinformatics tools, we evaluated the IG CDR3-MMP2 binding affinities throughout the cancer genome atlas breast cancer (TCGA-BRCA) dataset. Results: Results indicated that the better the CDR3-MMP2 binding, the better the survival probability. An analogous evaluation for four other proteases, including calpain-1 and thermolysin, displayed no such associations with survival probabilities. Conclusion: This study is consistent with the possibility that patient IG-cancer protease interactions could impact outcomes and raises the question of whether therapeutic antibody targeting of MMP2 would reduce breast cancer mediated tissue destruction and breast cancer mortality rates.

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“…Low granzyme B levels likely represent a lack of T-cell activation, in turn due to a lack of TCR binding to an epitope. In such cases, the immune microenvironment referred to above, supporting tumor growth (1,4), could be in effect.…”

Section: Developing Parameters For Application Of Anti-inflammatory T...mentioning

confidence: 99%

Time to consider sequencing anti-inflammatory treatments with chemotherapy and immuno-stimulation?

Blanck

2022

Front. Immunol.

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

Cited by 12 publications

References 26 publications

Electrostatic Complementarities of Glioblastoma-Resident T-Cell Receptors and Cancer Testis Antigens Linked to Poor Outcomes and High Levels of Sphingosine Kinase-2 Expression

Electrostatic Complementarities of Glioblastoma-Resident T-Cell Receptors and Cancer Testis Antigens Linked to Poor Outcomes and High Levels of Sphingosine Kinase-2 Expression

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

Time to consider sequencing anti-inflammatory treatments with chemotherapy and immuno-stimulation?

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