Daria S Myalik

The current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or may develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are believed to be significantly influenced by the tumor microenvironment through secretory factors and biased cell-cell interactions. To explore the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (draining LNs), and tumors in 14 patients with three human cancers. We demonstrated that draining LNs are differentially involved in the interaction with the tumor site, and that significant heterogeneity exists even between different parts of a single lymph node (LN). Next, we confirmed and elaborated upon previous observations regarding intratumoral immunoglobulin heterogeneity. We identified B cell receptor (BCR) clonotypes that were expanded in tumors relative to draining LNs and blood and observed that these tumor-expanded clonotypes were less hypermutated than non-expanded (ubiquitous) clonotypes. Furthermore, we observed a shift in the properties of complementarity-determining region 3 of the BCR heavy chain (CDR-H3) towards less mature and less specific BCR repertoire in tumor-infiltrating B-cells compared to circulating B-cells, which may indicate less stringent control for antibody-producing B cell development in tumor microenvironment (TME). In addition, we found repertoire-level evidence that B-cells may be selected according to their CDR-H3 physicochemical properties before they activate somatic hypermutation (SHM). Altogether, our work outlines a broad picture of the differences in the tumor BCR repertoire relative to non-tumor tissues and points to the unexpected features of the SHM process.

10.7554/elife.89506

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Systematic evaluation of intratumoral and peripheral BCR repertoires in three cancers

eLife (2025)

Sofia V Krasik Ekaterina A. Bryushkova Г. В. Шаронов Daria S Myalik Elizaveta V Shurganova

The current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or may develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are believed to be significantly influenced by the tumor microenvironment through secretory factors and biased cell-cell interactions. To explore the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (draining LNs), and tumors in 14 patients with three human cancers. We demonstrated that draining LNs are differentially involved in the interaction with the tumor site, and that significant heterogeneity exists even between different parts of a single lymph node (LN). Next, we confirmed and elaborated upon previous observations regarding intratumoral immunoglobulin heterogeneity. We identified B cell receptor (BCR) clonotypes that were expanded in tumors relative to draining LNs and blood and observed that these tumor-expanded clonotypes were less hypermutated than non-expanded (ubiquitous) clonotypes. Furthermore, we observed a shift in the properties of complementarity-determining region 3 of the BCR heavy chain (CDR-H3) towards less mature and less specific BCR repertoire in tumor-infiltrating B-cells compared to circulating B-cells, which may indicate less stringent control for antibody-producing B cell development in tumor microenvironment (TME). In addition, we found repertoire-level evidence that B-cells may be selected according to their CDR-H3 physicochemical properties before they activate somatic hypermutation (SHM). Altogether, our work outlines a broad picture of the differences in the tumor BCR repertoire relative to non-tumor tissues and points to the unexpected features of the SHM process.

breakpoint cluster region

10.7554/elife.89506.4

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Systematic evaluation of intratumoral and peripheral BCR repertoires in three cancers

Sofia V Krasik Ekaterina A. Bryushkova Г. В. Шаронов Daria S Myalik Elizaveta V Shurganova

The current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are thought to be significantly influenced by the tumor microenvironment in the form of secretory factors and biased cell-cell interactions. To address the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (DLN), and tumors in 17 patients with three human cancers. We show that DLNs are differentially involved in the interaction with the tumor site and that there is significant heterogeneity even between different parts of a single DLN. Next, we confirmed and elaborated upon previous observations of intratumoral immunoglobulin heterogeneity. We identified BCR clonotypes that were expanded in tumors relative to DLN and blood and observed that these tumor-expanded clonotypes were less hypermutated than non-expanded (ubiquitous) clonotypes. Furthermore, we observed a shift in BCR CDR-H3 properties towards less mature and less specific BCR repertoire in tumor-infiltrating B-cells compared to circulating B-cells, which may indicate less stringent control for antibody-producing B cell development in TME. In addition, we found repertoire-level evidence that B-cells may be selected according to their CDR-H3 physicochemical properties before they activate somatic hypermutation (SHM). Altogether, our work outlines a broad picture of the difference in the tumor BCR repertoire relative to non-tumor tissues and points to the unexpected features of the SHM process.

breakpoint cluster region

10.7554/elife.89506.1

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Author response: Systematic evaluation of intratumoral and peripheral BCR repertoires in three cancers

Sofia V Krasik Ekaterina A. Bryushkova Г. В. Шаронов Daria S Myalik Elizaveta V Shurganova

The current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are thought to be significantly influenced by the tumor microenvironment in the form of secretory factors and biased cell-cell interactions. To address the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (draining LNs), and tumors in 14 patients with three human cancers. We show that draining LNs are differentially involved in the interaction with the tumor site and that there is significant heterogeneity even between different parts of a single lymph node (LN). Next, we confirmed and elaborated upon previous observations of intratumoral immunoglobulin heterogeneity. We identified B cell receptor (BCR) clonotypes that were expanded in tumors relative to draining LNs and blood and observed that these tumor-expanded clonotypes were less hypermutated than non-expanded (ubiquitous) clonotypes. Furthermore, we observed a shift in the properties of complementarity-determining region 3 of a BCR heavy chain (CDR-H3) towards less mature and less specific BCR repertoire in tumor-infiltrating B-cells compared to circulating B-cells, which may indicate less stringent control for antibody-producing B cell development in tumor microenvironment (TME). In addition, we found repertoire-level evidence that B-cells may be selected according to their CDR-H3 physicochemical properties before they activate somatic hypermutation (SHM). Altogether, our work outlines a broad picture of the difference in the tumor BCR repertoire relative to non-tumor tissues and points to the unexpected features of the SHM process.

breakpoint cluster region

Affinity maturation

Hybridoma technology

10.7554/elife.89506.2.sa2

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Systematic evaluation of intratumoral and peripheral BCR repertoires in three cancers

Sofia V Krasik Ekaterina A. Bryushkova Г. В. Шаронов Daria S Myalik Elizaveta V Shurganova

The current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are thought to be significantly influenced by the tumor microenvironment in the form of secretory factors and biased cell-cell interactions. To address the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (draining LNs), and tumors in 14 patients with three human cancers. We show that draining LNs are differentially involved in the interaction with the tumor site and that there is significant heterogeneity even between different parts of a single lymph node (LN). Next, we confirmed and elaborated upon previous observations of intratumoral immunoglobulin heterogeneity. We identified B cell receptor (BCR) clonotypes that were expanded in tumors relative to draining LNs and blood and observed that these tumor-expanded clonotypes were less hypermutated than non-expanded (ubiquitous) clonotypes. Furthermore, we observed a shift in the properties of complementarity-determining region 3 of a BCR heavy chain (CDR-H3) towards less mature and less specific BCR repertoire in tumor-infiltrating B-cells compared to circulating B-cells, which may indicate less stringent control for antibody-producing B cell development in tumor microenvironment (TME). In addition, we found repertoire-level evidence that B-cells may be selected according to their CDR-H3 physicochemical properties before they activate somatic hypermutation (SHM). Altogether, our work outlines a broad picture of the difference in the tumor BCR repertoire relative to non-tumor tissues and points to the unexpected features of the SHM process.

breakpoint cluster region

Affinity maturation

Hybridoma technology

10.7554/elife.89506.2

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Systematic evaluation of intratumoral and peripheral BCR repertoires in three cancers

Sofia V Krasik Ekaterina A. Bryushkova Г. В. Шаронов Daria S Myalik Elizaveta V Shurganova

The current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or may develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are believed to be significantly influenced by the tumor microenvironment through secretory factors and biased cell-cell interactions. To explore the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (draining LNs), and tumors in 14 patients with three human cancers. We demonstrated that draining LNs are differentially involved in the interaction with the tumor site, and that significant heterogeneity exists even between different parts of a single lymph node (LN). Next, we confirmed and elaborated upon previous observations regarding intratumoral immunoglobulin heterogeneity. We identified B cell receptor (BCR) clonotypes that were expanded in tumors relative to draining LNs and blood and observed that these tumor-expanded clonotypes were less hypermutated than non-expanded (ubiquitous) clonotypes. Furthermore, we observed a shift in the properties of complementarity-determining region 3 of the BCR heavy chain (CDR-H3) towards less mature and less specific BCR repertoire in tumor-infiltrating B-cells compared to circulating B-cells, which may indicate less stringent control for antibody-producing B cell development in tumor microenvironment (TME). In addition, we found repertoire-level evidence that B-cells may be selected according to their CDR-H3 physicochemical properties before they activate somatic hypermutation (SHM). Altogether, our work outlines a broad picture of the differences in the tumor BCR repertoire relative to non-tumor tissues and points to the unexpected features of the SHM process.

10.7554/elife.89506.3

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A rare case of transplant hepatectomy for metachronous colorectal cancer metastasis (de novo)

Russian Journal of Transplantology and Artificial Organs (2024)

В. Е. Загайнов N. М. Kiselev Dmitry V Komarov С. А. Васенин Е. А. Ashimov

In the presented case, a patient who underwent liver transplant procedure for cirrhosis resulting from chronic hepatitis C was diagnosed with colorectal cancer 12 years after the operation. A combined treatment plan consisting of right hemicolectomy followed by nine cycles of adjuvant polychemotherapy using the FOLFOX6 regimen was performed. Seven months following the conclusion of treatment, 22×35 mm foci in segment 8 was detected as a sign of metastatic liver disease. The patient had a transplant hepatectomy. At present, the relapse-free survival is 22 months.

10.15825/1995-1191-2024-4-69-76

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Systematic evaluation of intratumoral and peripheral BCR repertoires in three cancers

bioRxiv (Cold Spring Harbor Laboratory) (2023)

Sofia V Krasik Ekaterina A. Bryushkova Г. В. Шаронов Daria S Myalik Elizaveta V Shurganova

Abstract The current understanding of humoral immune response in cancer patients suggests that tumors may be infiltrated with diffuse B cells of extra-tumoral origin or may develop organized lymphoid structures, where somatic hypermutation and antigen-driven selection occur locally. These processes are believed to be significantly influenced by the tumor microenvironment through secretory factors and biased cell-cell interactions. To explore the manifestation of this influence, we used deep unbiased immunoglobulin profiling and systematically characterized the relationships between B cells in circulation, draining lymph nodes (draining LNs), and tumors in 14 patients with three human cancers. We demonstrated that draining LNs are differentially involved in the interaction with the tumor site, and that significant heterogeneity exists even between different parts of a single lymph node (LN). Next, we confirmed and elaborated upon previous observations regarding intratumoral immunoglobulin heterogeneity. We identified B cell receptor (BCR) clonotypes that were expanded in tumors relative to draining LNs and blood and observed that these tumor-expanded clonotypes were less hypermutated than non-expanded (ubiquitous) clonotypes. Furthermore, we observed a shift in the properties of complementarity-determining region 3 of the BCR heavy chain (CDR-H3) towards less mature and less specific BCR repertoire in tumor-infiltrating B-cells compared to circulating B-cells, which may indicate less stringent control for antibody-producing B cell development in tumor microenvironment (TME). In addition, we found repertoire-level evidence that B-cells may be selected according to their CDR-H3 physicochemical properties before they activate somatic hypermutation (SHM). Altogether, our work outlines a broad picture of the differences in the tumor BCR repertoire relative to non-tumor tissues and points to the unexpected features of the SHM process.

breakpoint cluster region

Affinity maturation

Hybridoma technology

10.1101/2023.04.16.537028

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Daria S Myalik

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