Regulatory lymphocytes: the dice that resolve the tumor endgame

Abstract

A large number of cancer patients relapse after chemotherapeutic treatment. The immune system is capable of identifying and destroying cancer cells, so recent studies have highlighted the growing importance of using combinatorial chemotherapy and immunotherapy. However, many patients have innate or acquired resistance to immunotherapies. Long-term follow-up in a pooled meta-analysis exhibited long-term survival in approximately 20% of patients treated with immune checkpoint inhibitors or the adoptive transfer of chimeric T cells. It has been reported that high levels of immunoregulatory cells in cancer patients contribute to immunotherapy resistance via immunosuppression. Among the most important regulatory cell subtypes are the CD4 + T-regulatory cells (Tregs), identified by their expression of the well-characterized, lineage-specific transcription factor FOXP3. In addition to CD4 + Tregs, other regulatory cells present in the tumor microenvironment, namely CD8 + Tregs and IL10-producing B-regulatory cells (Bregs) that also modulate the immune response in solid and lymphoid tumors. These cells together have detrimental effects on tumor immune surveillance and anti-tumor immunity. Therefore, targeting these regulatory lymphocytes will be crucial in improving treatment outcomes for immunotherapy.

Tumor promoting roles of IL-10, TGF-β, IL-4, and IL-35: Its implications in cancer immunotherapy

“… 12 , 13 Although several other types of immune cells such as Th17, Th2, and dendritic cells may act as immune-suppressive in certain cancers, however, MDSCs, TAMs, Treg, and Breg cells are the prominent source of regulatory cytokines and dominate the tumor milieu. 14 – 17 These cells exert their suppressive functions via several mechanisms, but the secretion of immune-regulatory cytokines is a significant contributor to immune suppression among several other mechanisms. 2 , 9 These immune-regulatory cytokines show tumor-promoting characteristics by regulating intracellular signaling in cancer cells and immune cells present within the tumor milieu by an autocrine or positive feedback loop.…”

Using the Systemic Immune-Inflammation Index (SII) as a Mid-Treatment Marker for Survival among Patients with Stage-III Locally Advanced Non-Small Cell Lung Cancer (NSCLC)

“…Platelets bind internal cytokines with proinflammatory growth factors and directly mediate tumorigenesis and angiogenesis [59][60][61][62][63][64][65][66][67]. Lymphocytes, which are reduced by inflammation, typically play a role in destroying and disrupting cancer cell proliferation [68][69][70][71][72]. Neutrophils have been shown to inhibit the T-cell lymphocyte response to tumors and are important in advancing tumor growth and proliferation [73][74][75][76][77].…”

Evaluating the effects of curcumin nanomicelles on clinical outcome and cellular immune responses in critically ill sepsis patients: A randomized, double-blind, and placebo-controlled trial

“…B and T cells comprise the adaptive immune system responding to pathogens ( 8 ). B cells generate antibodies and plasma cells for long-term immunity, whereas T cells, namely gamma delta (γδ), CD8+, CD4+, and regulatory T cells (Tregs), create plasma cells and antibodies for long-term immunity ( 9 ). In addition to activating immune responses, the entry of pathogens into the body leads to the activation of various inflammatory pathways, namely NLRs, HMGB-1, and NF-κB ( 10 ).…”