Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Harnessing Antitumor CD4+ T Cells for Cancer Immunotherapy.

ABSTRACT: Over the past decades, CD4+ T cells have been considered as a supporting actor in the fields of cancer immunotherapy. Until recently, accumulating evidence has demonstrated the critical role of CD4+ T cells during antitumor immunity. CD4+ T cells can either suppress or promote the antitumor cytotoxic CD8+ T cell responses, either in secondary lymphoid organs or in the tumor. In this review, we provide an overview of the multifaceted role of different CD4+ T cell subsets in cancer immune response and their contribution during cancer therapies. Specifically, we focus on the latest progress regarding the impact of CD4+ T cell modulation on immunotherapies and other cancer therapies and discuss the prospect for harnessing CD4+ T cells to control tumor progression and prevent recurrence in patients.

SUBMITTER: Ben Khelil M

PROVIDER: S-EPMC8750687 | biostudies-literature | 2022 Jan

REPOSITORIES: biostudies-literature

ACCESS DATA

Json Xml

Publications

Harnessing Antitumor CD4+ T Cells for Cancer Immunotherapy.

Ben Khelil Myriam M Godet Yann Y Abdeljaoued Syrine S Borg Christophe C Adotévi Olivier O Loyon Romain R

Cancers 20220105 1

Over the past decades, CD4+ T cells have been considered as a supporting actor in the fields of cancer immunotherapy. Until recently, accumulating evidence has demonstrated the critical role of CD4+ T cells during antitumor immunity. CD4+ T cells can either suppress or promote the antitumor cytotoxic CD8+ T cell responses, either in secondary lymphoid organs or in the tumor. In this review, we provide an overview of the multifaceted role of different C ...[more]

PMID: 35008422

Similar Datasets

Harnessing neoantigen specific CD4 T cells for cancer immunotherapy.

Project description:The goal of precision immunotherapy is to direct a patient's T cell response against the immunogenic mutations expressed on their tumors. Most immunotherapy approaches to-date have focused on MHC class I-restricted peptide epitopes by which cytotoxic CD8+ T lymphocytes (CTL) can directly recognize tumor cells. This strategy largely overlooks the critical role of MHC class II-restricted CD4+ T cells as both positive regulators of CTL and other effector cell types, and as direct effectors of antitumor immunity. In this review, we will discuss the role of neoantigen specific CD4+ T cells in cancer immunotherapy and how existing treatment modalities may be leveraged to engage this important T cell subset.

| S-EPMC7793607 | biostudies-literature

Harnessing adaptive natural killer cells in cancer immunotherapy.

Project description:Natural killer (NK) cells are innate lymphocytes with a refined ability to recognize transformed cells through a broad array of activating receptors in combination with stochastically expressed inhibitory receptors that recognize MHC-class I. Recent advances in NK cell biology have revealed a high degree of functional plasticity that can be attributed to dynamic cell-to-cell interactions in concert with transcriptional and epigenetic reprogramming. Here, we discuss how new insights into the adaptive behavior of NK cells pave the way for next generation cell therapy based on guided differentiation and selective expansion of particularly cytotoxic NK cell subsets.

| S-EPMC5528731 | biostudies-other

Harnessing allogeneic CD4+ T cells to reinvigorate host endogenous antitumor immunity.

Project description:Immune checkpoint blockade (ICB) therapies developed over the past decade have been among the most promising approaches for the treatment of patients with advanced cancers. However, the overall objective response rate of ICB therapy for various cancers remains insufficient. Hence, novel strategies are required to improve the efficacy of immunotherapy for advanced cancers. The graft-versus-tumor (GVT) effect, which reflects strong antitumor immunity, is known to occur after allogeneic hematopoietic stem cell transplantation (HSCT). The GVT effect is mainly caused by transplanted donor lymphocytes that recognize and react to distinct alloantigens on tumor cells. In contrast, transplanted allogeneic cells can, in some instances, induce endogenous antitumor immunity in recipients if the graft has been rejected. Because of this ability, allogeneic cells have also been used to induce endogenous antitumor immunity without HSCT, and their beneficial immune response is referred to as the "allogenic effect." Here, we review the usefulness of allogeneic cells, particularly allogeneic CD4+ T cells, in cancer immunotherapy by highlighting their unique potential to induce host endogenous antitumor immunity.

| S-EPMC10694512 | biostudies-literature

Frenemies in the Microenvironment: Harnessing Mast Cells for Cancer Immunotherapy.

Project description:Tumor development, progression, and resistance to therapies are influenced by the interactions between tumor cells and the surrounding microenvironment, comprising fibroblasts, immune cells, and extracellular matrix proteins. In this context, mast cells (MCs) have recently emerged as important players. Yet, their role is still controversial, as MCs can exert pro- or anti-tumor functions in different tumor types depending on their location within or around the tumor mass and their interaction with other components of the tumor microenvironment. In this review, we describe the main aspects of MC biology and the different contribution of MCs in promoting or inhibiting cancer growth. We then discuss possible therapeutic strategies aimed at targeting MCs for cancer immunotherapy, which include: (1) targeting c-Kit signaling; (2) stabilizing MC degranulation; (3) triggering activating/inhibiting receptors; (4) modulating MC recruitment; (5) harnessing MC mediators; (6) adoptive transferring of MCs. Such strategies should aim to either restrain or sustain MC activity according to specific contexts. Further investigation would allow us to better dissect the multifaceted roles of MCs in cancer and tailor novel approaches for an "MC-guided" personalized medicine to be used in combination with conventional anti-cancer therapies.

| S-EPMC10303176 | biostudies-literature

Harnessing natural killer cells for cancer immunotherapy: dispatching the first responders.

Project description:Natural killer (NK) cells have crucial roles in the innate immunosurveillance of cancer and viral infections. They are 'first responders' that can spontaneously recognize abnormal cells in the body, rapidly eliminate them through focused cytotoxicity mechanisms and potently produce pro-inflammatory cytokines and chemokines that recruit and activate other immune cells to initiate an adaptive response. From the initial discovery of the diverse cell surface receptors on NK cells to the characterization of regulatory events that control their function, our understanding of the basic biology of NK cells has improved dramatically in the past three decades. This advanced knowledge has revealed increased mechanistic complexity, which has opened the doors to the development of a plethora of exciting new therapeutics that can effectively manipulate and target NK cell functional responses, particularly in cancer patients. Here, we summarize the basic mechanisms that regulate NK cell biology, review a wide variety of drugs, cytokines and antibodies currently being developed and used to stimulate NK cell responses, and outline evolving NK cell adoptive transfer approaches to treat cancer.

| S-EPMC10019065 | biostudies-literature

Harnessing TAGAP to improve immunotherapy for lung squamous carcinoma treatment by targeting c-Rel in CD4+ T cells.

Project description:Revealing the immunosenescence, particularly in CD4+ T cell function in lung squamous carcinoma (LUSC) assists in devising individual treatment strategies. This study identifies differentially expressed genes (DEGs) between ROS1 mutated (ROS1MUT) and wild-type (ROS1WT) LUSC samples from the TCGA database. Using WGCNA, immune-related DEGs (IRGs) were screened. Prognostic signatures derived from IRGs were used to compare immune infiltration, chemotherapy sensitivity, and immune-phenotyping score (IPS) between high- and low-risk subgroups. Hub gene abundance in different cell clusters was analyzed via Sc-seq. TAGAP overexpression or silencing was employed to assess its impact on cytokines production and differentiation of CD4+ T cells, downstream c-Rel expression, and tumor progression. High-risk subgroups exhibited decreased infiltration of natural killer, follicular helper T, and CD8+ T cells, but increased plasma, CD4+ memory resting T, and macrophage M2 cells. These subgroups were more sensitive to Sunitinib and CTLA4 blockade. TAGAP expression was significantly reduced in LUSC. Overexpressing TAGAP enhanced CD4+ T cells to produce cytokines, promoted differentiation into Th1/Th17 cells, inhibited Treg conversion, and suppressed LUSC cell phenotype in vitro. TAGAP overexpression in CD4+ T cells also inhibited LUSC tumor growth and boosted immune infiltration in vivo. TAGAP's effects on CD4+ T cells were partly reversed by c-Rel overexpression, highlighting TAGAP's role in rejuvenating CD4+ T cells and exerting anticancer effects by inhibiting c-Rel. This study elucidates the novel therapeutic potential of targeting TAGAP to modulate CD4+ T cell activity in immunotherapy for LUSC.

| S-EPMC11861500 | biostudies-literature

Harnessing NK cells for cancer immunotherapy: immune checkpoint receptors and chimeric antigen receptors.

Project description:Natural killer (NK) cells, key antitumor effectors of the innate immune system, are endowed with the unique ability to spontaneously eliminate cells undergoing a neoplastic transformation. Given their broad reactivity against diverse types of cancer and close association with cancer prognosis, NK cells have gained considerable attention as a promising therapeutic target for cancer immunotherapy. NK cell-based therapies have demonstrated favorable clinical efficacies in several hematological malignancies but limited success in solid tumors, thus highlighting the need to develop new therapeutic strategies to restore and optimize anti-tumor activity while preventing tumor immune escape. The current therapeutic modalities yielding encouraging results in clinical trials include the blockade of immune checkpoint receptors to overcome the immune-evasion mechanism used by tumors and the incorporation of tumor-directed chimeric antigen receptors to enhance NK cell anti-tumor specificity and activity. These observations, together with recent advances in the understanding of NK cell activation within the tumor microenvironment, will facilitate the optimal design of NK cell-based therapy against a broad range of cancers and, more desirably, refractory cancers. [BMB Reports 2021; 54(1): 44-58].

| S-EPMC7851441 | biostudies-literature

Harnessing Unconventional T Cells for Immunotherapy of Tuberculosis

Project description:Even if the incidence of tuberculosis (TB) has been decreasing over the last years, the number of patients with TB is increasing worldwide. The emergence of multidrug-resistant and extensively drug-resistant TB is making control of TB more difficult. Mycobacterium bovis bacillus Calmette–Guérin vaccine fails to prevent pulmonary TB in adults, and there is an urgent need for a vaccine that is also effective in patients with human immunodeficiency virus (HIV) coinfection. Therefore, TB control may benefit on novel therapeutic options beyond antimicrobial treatment. Host-directed immunotherapies could offer therapeutic strategies for patients with drug-resistant TB or with HIV and TB coinfection. In the last years, the use of donor lymphocytes after hematopoietic stem cell transplantation has emerged as a new strategy in the cure of hematologic malignancies in order to induce graft-versus leukemia and graft-versus-infection effects. Moreover, adoptive therapy has proven to be effective in controlling cytomegalovirus and Epstein-Barr virus reactivation in immunocompromised patients with ex vivo expanded viral antigen-specific T cells. Unconventional T cells are a heterogeneous group of T lymphocytes with limited diversity. One of their characteristics is that antigen recognition is not restricted by the classical major histocompatibility complex (MHC). They include CD1 (cluster of differentiation 1)–restricted T cells, MHC-related protein-1–restricted mucosal-associated invariant T (MAIT) cells, MHC class Ib–reactive T cells, and ?? T cells. Because these T cells are genotype-independent, they are also termed “donor unrestricted” T cells. The combined features of low donor diversity and the lack of genetic restriction make these cells suitable candidates for T cell–based immunotherapy of TB.

| S-EPMC7497315 | biostudies-literature

Neoantigen-specific cytotoxic Tr1 CD4 T cells suppress cancer immunotherapy.

Project description:CD4+ T cells can either enhance or inhibit tumour immunity. Although regulatory T cells have long been known to impede antitumour responses1-5, other CD4+ T cells have recently been implicated in inhibiting this response6,7. Yet, the nature and function of the latter remain unclear. Here, using vaccines containing MHC class I (MHC-I) neoantigens (neoAgs) and different doses of tumour-derived MHC-II neoAgs, we discovered that whereas the inclusion of vaccines with low doses of MHC-II-restricted peptides (LDVax) promoted tumour rejection, vaccines containing high doses of the same MHC-II neoAgs (HDVax) inhibited rejection. Characterization of the inhibitory cells induced by HDVax identified them as type 1 regulatory T (Tr1) cells expressing IL-10, granzyme B, perforin, CCL5 and LILRB4. Tumour-specific Tr1 cells suppressed tumour rejection induced by anti-PD1, LDVax or adoptively transferred tumour-specific effector T cells. Mechanistically, HDVax-induced Tr1 cells selectively killed MHC-II tumour antigen-presenting type 1 conventional dendritic cells (cDC1s), leading to low numbers of cDC1s in tumours. We then documented modalities to overcome this inhibition, specifically via anti-LILRB4 blockade, using a CD8-directed IL-2 mutein, or targeted loss of cDC2/monocytes. Collectively, these data show that cytotoxic Tr1 cells, which maintain peripheral tolerance, also inhibit antitumour responses and thereby function to impede immune control of cancer.

| S-EPMC11291290 | biostudies-literature

Harnessing epithelial-mesenchymal plasticity to boost cancer immunotherapy.

Project description:Immune checkpoint blockade (ICB) therapy is a powerful option for cancer treatment. Despite demonstrable progress, most patients fail to respond or achieve durable responses due to primary or acquired ICB resistance. Recently, tumor epithelial-to-mesenchymal plasticity (EMP) was identified as a critical determinant in regulating immune escape and immunotherapy resistance in cancer. In this review, we summarize the emerging role of tumor EMP in ICB resistance and the tumor-intrinsic or extrinsic mechanisms by which tumors exploit EMP to achieve immunosuppression and immune escape. We discuss strategies to modulate tumor EMP to alleviate immune resistance and to enhance the efficiency of ICB therapy. Our discussion provides new prospects to enhance the ICB response for therapeutic gain in cancer patients.

| S-EPMC10066239 | biostudies-literature