Role of B Cells in Responses to Checkpoint Blockade Immunotherapy and Overall Survival of Cancer Patients

Kim, Sangwoo S.; Sumner, Whitney; Miyauchi, Sayuri; Cohen, Ezra E.W.; Califano, Joseph A.; Sharabi, Andrew B.

doi:10.1158/1078-0432.ccr-21-0697

Cited by 54 publications

(51 citation statements)

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“…B cells can positively modulate antitumor immune responses by secretion of cytokines, production of antitumor antibodies, and presentation of antigens to T cells (1,(31)(32)(33)(34)(35). We noted that treatment with CpG and IL-12Fc also stimulated non-T immune (CD3 − ) cells (Fig.…”

Section: B Cells Are Activated and Essential For Antitumor Responsesmentioning

confidence: 77%

Intratumoral immunotherapy relies on B and T cell collaboration

et al. 2022

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Antitumor T cell responses are the primary mediators of cancer immunotherapy. However, many other components of the immune system are needed for efficient T cell responses to be generated. Here, we developed a combinatorial approach where a Toll-like receptor 9 agonist (CpG) and Fc-fused IL-12 protein were injected together into just one of several tumor sites in a mouse. This combination led to body-wide (abscopal) therapeutic responses in multiple cancer models. These systemic responses were dependent not only on T cells but also on B cells. B cells were activated by the treatment and were required for optimal T cell activation. This cross-talk was dependent on MHC and was tumor antigen specific. The addition of an agonistic antibody against OX40 further enhanced T cell activation and therapeutic responses. Our data suggest that the combination of CpG, anti-OX40, and IL-12Fc may have success in patients with cancer and that B and T cell collaboration is crucial for the efficacy of this combination immunotherapy.

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Section: B Cells Are Activated and Essential For Antitumor Responsesmentioning

confidence: 77%

Intratumoral immunotherapy relies on B and T cell collaboration

et al. 2022

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“…In the current study, we found that the decrease in circulating B cells was accompanied by an increase in Ig G, Ig κ, and Ig λ. B cells migrate from the bone marrow to the secondary lymphoid organs (SLOs) and undergo isotype switching to Ig G after being activated by antigens ( 18 , 35 ). Therefore, the reduction in circulating B cells may be due to the isotype switch to antibodies.…”

Section: Discussionmentioning

confidence: 99%

Transarterial Chemoembolization Combined With Immune Checkpoint Inhibitors and Tyrosine Kinase Inhibitors for Unresectable Hepatocellular Carcinoma: Efficacy and Systemic Immune Response

Yang

Huang

et al. 2022

Front. Immunol.

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BackgroundLocoregional therapy combined with systemic therapy can further improve the prognoses for HCC. However, the efficacy of TACE combined with ICIs and TKIs for HCC and whether this triple therapy can activate systemic immune response are still unknown.PurposeTo identify the efficacy of TACE+ICIs+TKIs for unresectable hepatocellular carcinoma (uHCC) and its effect on systemic immunity.Materials and MethodsThis single-center retrospective study was approved by the Institutional Review Board. From August 1, 2019, to March 30, 2021, patients with uHCC who received the combination therapy of TACE+ICIs+TKIs were included. Peripheral blood samples were collected at baseline and once a month for 4 months after treatment. Lymphocyte subsets were measured by flow cytometry. Immunoglobulins were measured using the immune turbidimetric method. The dynamic change trend of circulating parameters was tested using simple linear regression.ResultsFifty-three patients with a mean age of 59 ± 10.6 years were included. TTP was 8.0 months (95% CI, 5.5–10.5) and PFS was 8.5 months (95% CI, 5.4–11.5). ORR was 52.8% and DCR was 81.1%. Twenty patients had completed analysis of biomarkers in peripheral blood. For cellular immune response, the level of circulating CD8+, CD3+ T cells and NK cells increased, the frequency of CD4+T cells and the CD4+/CD8+ ratio decreased, and among them, CD8+ T cells increased significantly. For humoral immune response, there was a significant decrease in B cells and a significant increase in Ig G, Ig κ, and Ig λ. Moreover, Ig G, Ig κ, and Ig λ were related to tumor response.ConclusionTACE+ICIs+TKIs showed considerable efficacy in patients with uHCC. This triple therapy activated not only cell immune but also humoral immune activation. Circulating Ig G, Ig λ, and Ig κ can serve as potential biomarkers.

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“…While current cancer immunotherapeutic strategies focus extensively on augmentation of immune surveillance by T cells, the role of B cells in cancer has only begun to emerge in recent years. Tumor-infiltrating B cells exert both antitumor and protumor effects, depending on their immunestimulatory or immune-suppressive activities, which vary with cancer type (1,2). A meta-analysis of 69 studies in 19 cancers showed a positive association of B cell infiltration with favorable prognosis in half of the studies, compared with less than 10% of studies showing a negative association (3).…”

Section: B Cells Can Exert Antitumor Activitymentioning

confidence: 99%

“…B cells can exert antitumor activity via production of antibodies against tumorassociated antigens (TAAs). Antibodies in turn can impact downstream immune responses, including antibody-dependent cellular cytotoxicity (ADCC) by NK cells, phagocytosis by macrophages (ADCP), and antigen presentation and T cell priming by dendritic cells (DCs) (1,2). B cells express MHC II to directly serve as antigenpresenting cells, triggering T cell activation, including that of T follicular helper cells (5)(6)(7).…”

Section: B Cells Can Exert Antitumor Activitymentioning

confidence: 99%