Malignant tumors have become a major threat to human life and a huge health burden in the 21 century, with approximately 10 million deaths worldwide from malignant neoplasms in the past few years (Siegel et al., 2021). Promisingly, cancer mortality has continued to decline since 1991 with improvements in early detection and management (Torre et al., 2016). Cancer immunotherapy, one of the breakthroughs in cancer treatment, has played a prominent role in the steady decline in cancer mortality in recent decades (Yang, 2015). Named a "Top 10 Scientific Breakthroughs" by Science magazine in 2013, it is receiving increasing attention in cancer treatments (Couzin-Frankel, 2013). In particular, the successful clinical application of immune checkpoint inhibitor (ICI) and chimeric antigen receptor T (CAR-T) cell therapies opens up new possibilities for cancer treatment.They induce lasting tumor remissions in patients with various advanced cancers (Cloughesy et al., 2019, Rotte, 2019). But they are also limited by the indecisive effectiveness and lower response rates due to the complicated tumor immune microenvironment (TIME) varied from different kinds of tumors, even among different cancer patients (Van den Bossche et al., 2022). With the deepening research on TIME, increased immune-related biomarkers have been identified to predict the cancer sensitivity and theraputic effect of immunotherapy (Ayers et al., 2017, Cho et al., 2020). Immunotherapy, therefore, remains challenging, but also promising.

Immunocytes are the cellular basis of immunotherapies and are key players in providing strategies for cancer development and progression. Therefore, decoding the different immune infiltrations in the tumor microenvironment (TME) is necessary to improving therapeutic response rates and developing novel treatment strategies. Immunoinfiltration in TME consists mainly of T lymphocytes, B lymphocytes, macrophages, dendritic cells, natural killer cells, mast cells, and neutrophils (Fridman et al., 2017). T lymphocytes have been the investigating focus in the TME in the past decades due to their prominent tumor-killing capability (Okła et al., 2021, Maimela et al., 2019, Stanton and Disis, 2016). Abundant research has shown that T lymphocyte phenotypes such as CD3+, CD8+, and CD4 + T lymphocytes are correlated with favorable prognoses in multiple solid tumors (Fridman et al., 2011, de Ruiter et al., 2017). In contrast, the role of B-lymphocytes in the TME has not been well studied until important studies in recent years have highlighted its potentially significant impact on cancer immunotherapy (Helmink et al., 2020, Petitprez et al., 2020, Cabrita et al., 2020). Two back-to-back studies found that B cell signatures were the most differently expressed genes between responders versus non-responders who received ICI treatment in melanoma patients. And it is significantly enriched in the responders (Helmink et al., 2020, Cabrita et al., 2020). They revealed the B lymphocytes in the TME act as antigen-presenting cells, secrete antibodies and a series of cytokines against tumor cells. They also drive the function and expansion of tumor-associated T cell responses, implying an important role for B lymphocytes in TME. However, since relatively few studies have focused on the prognostic value of the B lymphocytes for cancer patients, and the role of tumor-infiltrating B lymphocytes (TIBLs) and plasma cells (PCs) in TME remains controversial, due to the complicated components and cellular interactions of TME (Patel et al., 2020, Cai et al., 2019, Sarvaria et al., 2017). Therefore, it is timely and necessary to determine the specific prognostic impact of B lymphocytes in solid malignancies.

In this study, we performed a comprehensive and systematic literature review to identify all published studies evaluating the prognostic role of TIBLs in solid tumors, involving common neoplasms from the respiratory, digestive, urinary, and reproductive systems. As we focused on the role of B cells lymphocytes in TME, we only reviewed the studies in which B cells were detected in situ in tumor tissue by immunohistochemistry (IHC) or immunofluorescence (IF)

methods. Next, we combined eligible quantitative data in a meta-analysis, and also summarized the conclusion for those not meet the inclusion criteria of the meta-analysis. Finally, the role of TIBLs in the immunotherapy of cancer patients is reviewed and analyzed. This study is aimed to elucidate the exact relationship between TIBLs and prognosis in different cancer patients and to

provide the reference on how to manage these cells for the immunotherapies for cancer patients in

the future clinic practice.