Review
Significance of intratumoral infiltration of B cells in cancer immunotherapy: From a single cell perspective

https://doi.org/10.1016/j.bbcan.2021.188632Get rights and content

Abstract

Immunotherapy for cancer has provided new treatment approaches for malignant tumors, but there are low rates of response and high rates of resistance. The most recent sequencing method which is called single-cell RNA sequencing(scRNA-seq) determines the transcriptome at the single cell level, which allows high-resolution dynamic monitoring of the tumor microenvironment (TME) during immunotherapy. As an important part of humoral immunity, tumor-infiltrated B cells have been reported to have distinct functions in anti-tumor immunity, which are characterized by their RNA transcriptome, membrane surface receptors, and immunoglobulin secretion, suggesting great immunotherapeutic effects. On the basis of the important roles of B cells in immunotherapy reported in recent publications, we discuss the tumor-infiltrated B cells' subpopulations, differentiation trajectory, and interactions with other cells in the TME in this review, hoping to illustrate its significance in potential clinical application as biomarkers and therapeutic targets.

Section snippets

Background

The emergence of immunotherapy, such as immune checkpoint blockade (ICB) [1], personalized tumor vaccines [2], and oncolytic virus therapies [3], is a milestone in the history of anti-tumor therapy. Unfortunately, immunotherapy is only effective for limited cancer types and patients are likely to develop resistance in a short period of time [4]. The most recent study showed high tumor mutation burden could not act as a precise biomarker to predict ICB response in most solid cancers [5].

Targeting the transcriptome to explore B cell diversity

Single cell sequencing allows further exploration of intratumoral heterogeneity. Unlike flow cytometry, mass spectrometry, or any other previous method, single cell sequencing is a continuous rather than discrete approach [26]. The steps of scRNA-seq mainly include the following four steps: (1) isolation of single cells, (2) reverse transcription into cDNA, (3) cDNA amplification by PCR, and (4) sequencing library construction (Fig. 1a) [27]. Fluorescence-activated cell sorting (FACS) could be

Model of B cell maturation and differentiation

Peripheral immature B cells enter B lymphoid follicles through high endothelial veins [47]. In B cell follicles, naïve B cells (CD27−) encounter antigens through resident APCs, which include DCs and follicular dendritic cells (FDCs), after which activation of BCR signaling induces antigen extraction, internalization, and processing to present the peptide on MHC II. Then, B cells migrate to the border of the follicle zone, which is adjacent to the T cell zone, to present the antigen to

B cell subpopulations in tumors

Usually, according to the differentiation progression, B cells could be divided into naïve B cells, MBCs and ASCs and they each have distinct phenotypes and functions in TME (Table 2). In mapping the immune cell landscape of cancer, due to the low percentage of B cells in specific cancers, they are often divided into CD19+ CD20+ B cells and CD138 + SDC1 + PCs [15], [72]. The scRNA-seq analysis targeting at TIL-Bs reduced the dimensions of these cells to a higher resolution, resulting in more

B and T cells

As the best partners, B and T cells work together to regulate and differentiate with each other, which is shown by co-infiltration of abundant B and T cells into the TLS structure (Fig. 3) [19]. Jh−/− mice without mature B cells show decreases of CD4+ and CD8+ T cells and an increase of the Treg cells phenotype [79]. In the single cell analysis of ovarian cancer, samples with more T cells infiltration showed more abundant clusters of distinct B cells infiltrated in TME [74]. Single cell

Conclusions

On the basis of the important regulation roles of TIL-Bs in TME, the latest sequencing technology at single cell level characterize them in terms of RNA transcriptome, BCR and immunoglobulin. The scRNA-seq studies summarized in this review reveals the heterogeneity of differentiation and distribution of B cell subpopulations and their interactions with other cells in TME, establishing an integral role for TIL-Bs in response to immunotherapy. Our review is expected to help facilitate the

Ethics approval and consent to participate

Not applicable.

Consent for publication

Not applicable.

Availability of data and materials

All data generated or analysed during this study are included in this published article.

Funding

This work was financially supported by the National Natural Science Foundation of China (82025035, 81871989); the Shanghai Science and Technology Committee Program (19XD1420900) and Shanghai Education Commission Program (17SG04).

Authors' contributions

SG drafted the manuscript. LQ, YZ, KC, YL and JW provided constructive suggestions and revised the manuscript. PW designed the study and revised the manuscript. All the authors read and approved the final manuscript.

Declaration of Competing Interest

The authors declare that they have no competing interests.

Acknowledgment

Some of the figures are created with BioRender.com.

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