Heterogeneity and Functions of Tumor-Infiltrating Antibody Secreting Cells: Lessons from Breast, Ovarian, and Other Solid Cancers.

Neglected for a long time in cancer, B cells and ASCs have recently emerged as critical actors in the tumor microenvironment, with important roles in shaping the antitumor immune response. ASCs indeed exert a major influence on tumor growth, patient survival, and response to therapies. The mechanisms underlying their pro- vs. anti-tumor roles are beginning to be elucidated, revealing the contributions of their secreted antibodies as well as of their emerging noncanonical functions. Here, concentrating mostly on ovarian and breast cancers, we summarize the current knowledge on the heterogeneity of tumor-infiltrating ASCs, we discuss their possible local or systemic origin in relation to their immunoglobulin repertoire, and we review the different mechanisms by which antibody (Ab) subclasses and isoforms differentially impact tumor cells and anti-tumor immunity. We also discuss the emerging roles of cytokines and other immune modulators produced by ASCs in cancer. Finally, we propose strategies to manipulate the tumor ASC compartment to improve cancer therapies.

Neoadjuvant immune checkpoint inhibitors in cancer, current state of the art.

Immunotherapy has been a revolution in cancer management in the metastatic setting. This has led to a prompt evaluation of such therapies in earlier stages. This article discusses the still limited amount of data finding the rationale to assess such therapy in this setting and reviews preclinical and clinical data available. Overall, neoadjuvant immunotherapy is a promising approach for the treatment of cancers and the rationale supporting its use is strong. Neoadjuvant immunotherapy resulted, in the majority of clinical trials, in improved pathologic complete response rates with a favorable toxicity profile and no delay in surgery. Various regimens were effective: inhibitory immune check-point blockers (IICPB) alone, combination of PD-1 and CTLA-4 inhibitors, combination of chemotherapy (CT) and IICPB, phased CT and IICPB (either IICPB before CT or IICPB after CT). Yet the question whether neoadjuvant immunotherapy will benefit to patients in terms of disease-free and, ultimately, overall survival remains unknown.