scholarly journals Early disappearance of tumor antigen-reactive T cells from peripheral blood correlates with superior clinical outcomes in melanoma under anti-PD-1 therapy

2021 ◽  
Vol 9 (12) ◽  
pp. e003439
Author(s):  
Jonas Bochem ◽  
Henning Zelba ◽  
Janine Spreuer ◽  
Teresa Amaral ◽  
Andrea Gaissler ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Metastatic Melanoma ◽  
Clinical Outcomes ◽  
Peripheral Blood ◽  
Intracellular Cytokine Staining ◽  
Digital Pathology ◽  
Stage Iv ◽  
Predictive Biomarkers ◽  
Immune Checkpoint Blockade

BackgroundAnti-programmed cell death protein 1 (PD-1) antibodies are now routinely administered for metastatic melanoma and for increasing numbers of other cancers, but still only a fraction of patients respond. Better understanding of the modes of action and predictive biomarkers for clinical outcome is urgently required. Cancer rejection is mostly T cell-mediated. We previously showed that the presence of NY-ESO-1-reactive and/or Melan-A-reactive T cells in the blood correlated with prolonged overall survival (OS) of patients with melanoma with a heterogeneous treatment background. Here, we investigated whether such reactive T cells can also be informative for clinical outcomes in metastatic melanoma under PD-1 immune-checkpoint blockade (ICB).MethodsPeripheral blood T cell stimulation by NY-ESO-1 and Melan-A overlapping peptide libraries was assessed before and during ICB in two independent cohorts of a total of 111 patients with stage IV melanoma. In certain cases, tumor-infiltrating lymphocytes could also be assessed for such responses. These were characterized using intracellular cytokine staining for interferon gamma (IFN-γ), tumor negrosis factor (TNF) and CD107a. Digital pathology analysis was performed to quantify NY-ESO-1 and Melan-A expression by tumors. Endpoints were OS and progression-free survival (PFS).ResultsThe initial presence in the circulation of NY-ESO-1- or Melan-A-reactive T cells which became no longer detectable during ICB correlated with validated, prolonged PFS (HR:0.1; p>0.0001) and OS (HR:0.2; p=0.021). An evaluation of melanoma tissue from selected cases suggested a correlation between tumor-resident NY-ESO-1- and Melan-A-reactive T cells and disease control, supporting the notion of a therapy-associated sequestration of cells from the periphery to the tumor predominantly in those patients benefitting from ICB.ConclusionsOur findings suggest a PD-1 blockade-dependent infiltration of melanoma-reactive T cells from the periphery into the tumor and imply that this seminally contributes to effective treatment.

Adoptive T-cell therapy (ACT) with TILs for metastatic melanoma: Clinical responses and durable persistence of anticancer responses in peripheral blood.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. 3028-3028 ◽  
Author(s):  
Marco Donia ◽  
Rikke Andersen ◽  
Eva Ellebaek ◽  
Trine Zeeberg Iversen ◽  
Mads Hald Andersen ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Metastatic Melanoma ◽  
Peripheral Blood ◽  
Intracellular Cytokine Staining ◽  
Adoptive T Cell Therapy ◽  
Medium Size ◽  
T Cell Therapy ◽  
Hematopoietic Stem ◽  
Clinical Responses

3028 Background: TIL treatment holds the promise to introduce a new treatment paradigm into oncology practice. To demonstrate the logistical feasibility of this complex approach in Europe, at Herlev Hospital, Denmark, we have initiated a trial for patients with metastatic melanoma and evaluated the melanoma-specific immunity in the peripheral blood. Methods: We present the updated results of trial NCT00937625. The study takes place in a medium-size academic center (30 in-patient oncology beds) equipped with a 36 square meters cGMP cell production lab integrated in a hematopoietic stem cell transplantation unit. Patients were treated with autologous TILs preceded by standard lymphodepleting chemotherapy but followed by attenuated regimens of IL-2 (n=6 low-dose s.c. for 14 days; n=9 i.v. intermediate decrescendo dose). Melanoma-specific responses were assessed with intracellular cytokine staining. Results: We have generated TILs from 28/31 patients, with 15 patients treated so far and many TILs cryopreserved for future use. Patients were treated with an average of >50x109 CD4+, CD8+and a small but consistent fraction of γδ TILs. The lower doses of IL-2 have significantly decreased the classical toxicity of the treatment associated with more harsh IL-2 regimens, and response evaluation showed the achievement of three CR lasting > 1 year and four PR. Clinical responses were associated with high numbers of tumour reactive T-cells infused. Importantly, in most responding patients we observed induction and durable persistence (up to 1 year) of anti-melanoma T-cell responses in the peripheral blood. Conclusions: A high response rate including durable complete responses can be induced after treatment with TILs followed by an attenuated regimen of IL-2, which significantly reduced the occurrence of severe side effects. Effective TIL treatment is associated with induction and long-term persistence in the blood of T cells producing in vitro anticancer responses. By showing that TIL-based ACT is logistically feasible and accessible to medium-size academic centers, we open the possibility for testing this treatment in a large randomized setting in Europe. Clinical trial information: NCT00937625.

Myeloid-derived suppressor cell quantity prior to treatment with ipilimumab at 10mg/kg to predict for overall survival in patients with metastatic melanoma.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 2518-2518 ◽  
Author(s):  
Shigehisa Kitano ◽  
Michael Andrew Postow ◽  
Czrina Cortez ◽  
Teresa Rasalan ◽  
Humilidad F. Gallardo ◽  
...  
Keyword(s):  
Cell Proliferation ◽  
Overall Survival ◽  
T Cell ◽  
Metastatic Melanoma ◽  
Peripheral Blood ◽  
Clinical Benefit ◽  
Stage Iv ◽  
T Cell Proliferation ◽  
Pre Treatment

2518 Background: Ipilimumab, an antibody that blocks the function of the immune inhibitory molecule cytotoxic T lymphocyte antigen 4 (CTLA-4), significantly prolongs survival in patients with metastatic melanoma. Approximately 30% of patients derive clinical benefit from therapy. Defining biomarkers of response to ipilimumab therapy would enable selection of patients more likely to respond and is relevant for both practicing clinicians and for clinical trial design. We performed a pilot correlative study evaluating myeloid derived suppressor cells (MDSC), a population of immune suppressive monocytic cells, as a biomarker of clinical outcome. Methods: Peripheral blood from 26 patients with stage IV melanoma treated with ipilimumab 10mg/kg every 3 weeks for 4 doses at our center, as part of an expanded access program (BMS CA184-045) was assessed for MDSC quantity (%CD14+,HLA-DRlow/- cells) pre-treatment, at week 7, week 12, and week 24 by flow cytometry. MDSC ability to inhibit T cell proliferation was tested using an in vitro suppression assay. Results: We found that lower MDSC quantity pre-treatment predicted for improved overall survival (Hazard ratio 1.07 (1.03, 1.11) p=0.002) and trended toward associating with clinical benefit measured at week 24 imaging (p=0.09). This effect was independent of pre-treatment or week 7 absolute lymphocyte counts (ALC) and pre-treatment LDH when evaluated in a multivariate model with ALC and MDSC quantity HR 1.10; 95% CI 1.04, 1.17 p=0.0006 and LDH and MDSC quantity HR 1.06; 95% CI 1.01, 1.11 p = 0.013. Furthermore, a general trend of increasing MDSC number by week 24 from the pre-treatment baseline was associated with patients that did not achieve clinical benefit. MDSC suppressed peripheral blood T cell proliferation as measured by CFSE dilution in response to anti-CD3 antibody stimulation. Conclusions: Pre-treatment MDSC quantity may predict clinical response following ipilimumab therapy. Further studies evaluating MDSC as a biomarker of ipilimumab therapy are warranted both retrospectively and prospectively in a broader group of patients.

Association of an RNA signature (RS) with emergence of ICOS hi CD4 T cells and efficacy outcomes for the ICOS agonist vopratelimab (vopra) and nivolumab (nivo) in patients (pts) on the ICONIC trial.

2020 ◽  
Vol 38 (5_suppl) ◽  
pp. 14-14
Author(s):  
Timothy A Yap ◽  
Justin F. Gainor ◽  
Howard A. Burris ◽  
Shivaani Kummar ◽  
Russell Kent Pachynski ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Clinical Outcomes ◽  
Cd4 T Cells ◽  
Costimulatory Molecule ◽  
Predictive Biomarkers ◽  
Cd4 T Cell ◽  
Effector Cells ◽  
T Effector Cells ◽  
Tumor Biopsies

14 Background: ICOS is a costimulatory molecule upregulated on activated T cells. Vopra is an investigational ICOS agonist antibody that results in activation and proliferation of primed CD4 T effector cells. Vopra was assessed in heavily pretreated patients with advanced solid tumors as monotherapy (mono) or in combination with nivolumab (nivo) in the Phase 1/2 ICONIC trial (NCT02904226). Emergence of a distinct ICOS high (hi) population of peripheral CD4 T effector cells, not seen with PD-1 inhibitors alone, was associated with improved ORR, PFS and OS with vopra mono and combo therapy (AACR 2019). Baseline tumor and blood biomarkers were assessed for ability to predict ICOS hi CD4 T cell emergence and clinical outcomes. Methods: Fresh pre-treatment tumor biopsies were assessed by RS, a gene signature describing immune cell infiltration, and other biomarkers, including PD-L1 TPS by IHC. Pts were classified as RS1 and RS2 based on medium and high cutoffs. Associations between potential predictive biomarkers, ICOS hi CD4 T cell emergence and clinical outcomes were evaluated. Results: Baseline RS is significantly higher in patients with emergence of ICOS hi CD4 T cells. High RS was associated with increased emergence of ICOS hi CD4 T cells, accompanied by improved RECIST response, PFS, and OS. In contrast, no association was noted with PD-L1 IHC. Clinical trial information: NCT02904226. Conclusions: In this retrospective subset analysis, the RS score, but not PD-L1, in baseline tumor biopsies was predictive of emergence of an ICOS hi CD4 T cell population and improved RECIST response, PFS, and OS in patients treated with vopra alone and in combination with nivo. Clinical evaluation of vopra and investigational PD-1 inhibitor JTX-4014 in cancer patients with RS selection is planned. [Table: see text]

scholarly journals 289 PGV-001: a phase 1 trial of a personalized neoantigen peptide vaccine for the treatment of malignancies in the adjuvant setting

2020 ◽  
Vol 8 (Suppl 3) ◽  
pp. A316-A316
Author(s):  
Thomas Marron ◽  
Julia Kodysh ◽  
Alex Rubinsteyn ◽  
John Finnigan ◽  
Ana Blazquez ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Peripheral Blood ◽  
Ex Vivo ◽  
Phase 1 ◽  
Intracellular Cytokine Staining ◽  
Peptide Vaccine ◽  
Mount Sinai Hospital ◽  
Adjuvant Setting

BackgroundThe efficacy of T cell directed immunotherapies relies on adequate priming of T cells to tumor-specific neoantigens, which some studies have augmented with synthetic neoantigen vaccines. This is the first report of a personalized genomic vaccine (PGV-001) in multiple histologies in the adjuvant setting.MethodsTumor and germline RNA and DNA were sequenced, and neoantigen peptides were selected using our OpenVax custom computation pipeline that identifies and ranks mutant sequences by a combination of predicted MHC-I binding affinity and neoantigen abundance within tumor. Up to 10 peptides were synthesized per patient and were administered over the course of 27 weeks in combination with the poly-ICLC. Primary objectives were to determine 1) the safety and tolerability; 2) the feasibility of PGV-001 production and administration; and 3) the immunogenicity of PGV-001. Secondary objectives included immunophenotyping neoantigen-specific T cells in peripheral blood, and characterization of peripheral blood lymphoid, myeloid and humoral responses. We report here for the first time on the primary endpoints.ResultsVaccine was synthesized for 15 patients. A mean of 1619 somatic variants (range 521–5106) were detected. Our pipeline identified a mean of 67.1 neoantigens/patient (range 8–193) and 9.7 peptides/patient were synthesized (range 7–10). 13 patients received PGV-001 (11 patients received all 10 doses and 2 patients received at least 8 doses) while 2 had progressive disease before vaccine initiation. Transient grade 1 injection site reactions were seen in 31% of patients, and one patient experienced grade 1 fever. There were no other significant adverse events. Ex vivo ELISpot analysis of patient blood demonstrated significant induction of T cell responses following receipt of 10 vaccines that were not present after the 6th vaccine, supporting the need for a prolonged dosing schedule. Robust responses were seen in both CD4 and CD8 T cells by intracellular cytokine staining for TNF-a, IFN-a, and IL-2 following in vitro expansion in the presence of vaccine antigens. Additional studies are ongoing to define the most immunogenic antigens.ConclusionsA personalized neoantigen vaccine of synthetic mutant peptides and adjuvant poly-ICLC was successfully synthesized for 15 patients and administered successfully to 87% patients over the course of 27 weeks. The vaccine was well tolerated, and T cell expansion and reactivity to synthetic neoantigens confirms immunogenicity of neoantigens identified with OpenVax.Trial RegistrationNCT02721043Ethics ApprovalThis study was approved by the IRB of The Mount Sinai Hospital in accordance with Federal law. HSM #15-00841.

scholarly journals Tumor infiltrating lymphocytes (TIL) therapy in metastatic melanoma: boosting of neoantigen-specific T cell reactivity and long-term follow-up

2020 ◽  
Vol 8 (2) ◽  
pp. e000848 ◽  
Author(s):  
Joost H van den Berg ◽  
Bianca Heemskerk ◽  
Nienke van Rooij ◽  
Raquel Gomez-Eerland ◽  
Samira Michels ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Metastatic Melanoma ◽  
Peripheral Blood ◽  
Tumor Infiltrating Lymphocytes ◽  
Phase Iii ◽  
Cell Reactivity ◽  
T Cell Reactivity ◽  
Infiltrating Lymphocytes

Treatment of metastatic melanoma with autologous tumor infiltrating lymphocytes (TILs) is currently applied in several centers. Robust and remarkably consistent overall response rates, of around 50% of treated patients, have been observed across hospitals, including a substantial fraction of durable, complete responses.PurposeExecute a phase I/II feasibility study with TIL therapy in metastatic melanoma at the Netherlands Cancer Institute, with the goal to assess feasibility and potential value of a randomized phase III trial.ExperimentalTen patients were treated with TIL therapy. Infusion products and peripheral blood samples were phenotypically characterized and neoantigen reactivity was assessed. Here, we present long-term clinical outcome and translational data on neoantigen reactivity of the T cell products.ResultsFive out of 10 patients, who were all anti-PD-1 naïve at time of treatment, showed an objective clinical response, including two patients with a complete response that are both ongoing for more than 7 years. Immune monitoring demonstrated that neoantigen-specific T cells were detectable in TIL infusion products from three out of three patients analyzed. For six out of the nine neoantigen-specific T cell responses detected in these TIL products, T cell response magnitude increased significantly in the peripheral blood compartment after therapy, and neoantigen-specific T cells were detectable for up to 3 years after TIL infusion.ConclusionThe clinical results from this study confirm the robustness of TIL therapy in metastatic melanoma and the potential role of neoantigen-specific T cell reactivity. In addition, the data from this study supported the rationale to initiate an ongoing multicenter phase III TIL trial.

scholarly journals A bilateral tumor model identifies transcriptional programs associated with patient response to immune checkpoint blockade

2020 ◽  
Vol 117 (38) ◽  
pp. 23684-23694
Author(s):  
Ivy X. Chen ◽  
Kathleen Newcomer ◽  
Kristen E. Pauken ◽  
Vikram R. Juneja ◽  
Kamila Naxerova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
T Cell Activation ◽  
Immune Checkpoint ◽  
Predictive Biomarkers ◽  
Tumor Model ◽  
Immune Checkpoint Blockade ◽  
Checkpoint Blockade ◽  
Patient Response ◽  
Bilateral Tumor

Immune checkpoint blockade (ICB) is efficacious in many diverse cancer types, but not all patients respond. It is important to understand the mechanisms driving resistance to these treatments and to identify predictive biomarkers of response to provide best treatment options for all patients. Here we introduce a resection and response-assessment approach for studying the tumor microenvironment before or shortly after treatment initiation to identify predictive biomarkers differentiating responders from nonresponders. Our approach builds on a bilateral tumor implantation technique in a murine metastatic breast cancer model (E0771) coupled with anti-PD-1 therapy. Using our model, we show that tumors from mice responding to ICB therapy had significantly higher CD8+T cells and fewer Gr1+CD11b+myeloid-derived suppressor cells (MDSCs) at early time points following therapy initiation. RNA sequencing on the intratumoral CD8+T cells identified the presence of T cell exhaustion pathways in nonresponding tumors and T cell activation in responding tumors. Strikingly, we showed that our derived response and resistance signatures significantly segregate patients by survival and associate with patient response to ICB. Furthermore, we identified decreased expression of CXCR3 in nonresponding mice and showed that tumors grown inCxcr3−/−mice had an elevated resistance rate to anti-PD-1 treatment. Our findings suggest that the resection and response tumor model can be used to identify response and resistance biomarkers to ICB therapy and guide the use of combination therapy to further boost the antitumor efficacy of ICB.

scholarly journals Regulatory T Cells Fail to Suppress Fast Homeostatic Proliferation In Vitro

Life ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 245
Author(s):  
Daniil Shevyrev ◽  
Valeriy Tereshchenko ◽  
Elena Blinova ◽  
Nadezda Knauer ◽  
Ekaterina Pashkina ◽  
...  
Keyword(s):  
Rheumatoid Arthritis ◽  
T Cells ◽  
T Cell ◽  
Regulatory T Cells ◽  
Autoimmune Diseases ◽  
Peripheral Blood ◽  
Treg Cells ◽  
Homeostatic Proliferation ◽  
Suppressive Activity ◽  
Healthy Donors

Homeostatic proliferation (HP) is a physiological process that reconstitutes the T cell pool after lymphopenia involving Interleukin-7 and 15 (IL-7 and IL-15), which are the key cytokines regulating the process. However, there is no evidence that these cytokines influence the function of regulatory T cells (Tregs). Since lymphopenia often accompanies autoimmune diseases, we decided to study the functional activity of Tregs stimulated by HP cytokines from patients with rheumatoid arthritis as compared with that of those from healthy donors. Since T cell receptor (TCR) signal strength determines the intensity of HP, we imitated slow HP using IL-7 or IL-15 and fast HP using a combination of IL-7 or IL-15 with anti-CD3 antibodies, cultivating Treg cells with peripheral blood mononuclear cells (PBMCs) at a 1:1 ratio. We used peripheral blood from 14 patients with rheumatoid arthritis and 18 healthy volunteers. We also used anti-CD3 and anti-CD3 + IL-2 stimulation as controls. The suppressive activity of Treg cells was evaluated in each case by the inhibition of the proliferation of CD4+ and CD8+ cells. The phenotype and proliferation of purified CD3+CD4+CD25+CD127lo cells were assessed by flow cytometry. The suppressive activity of the total pool of Tregs did not differ between the rheumatoid arthritis and healthy donors; however, it significantly decreased in conditions close to fast HP when the influence of HP cytokines was accompanied by anti-CD3 stimulation. The Treg proliferation caused by HP cytokines was lower in the rheumatoid arthritis (RA) patients than in the healthy individuals. The revealed decrease in Treg suppressive activity could impact the TCR landscape during lymphopenia and lead to the proliferation of potentially self-reactive T cell clones that are able to receive relatively strong TCR signals. This may be another explanation as to why lymphopenia is associated with the development of autoimmune diseases. The revealed decrease in Treg proliferation under IL-7 and IL-15 exposure can lead to a delay in Treg pool reconstitution in patients with rheumatoid arthritis in the case of lymphopenia.

scholarly journals Traditional Thai Massage Promoted Immunity in the Elderly via Attenuation of Senescent CD4+ T Cell Subsets: A Randomized Crossover Study

2021 ◽  
Vol 18 (6) ◽  
pp. 3210
Author(s):  
Kanda Sornkayasit ◽  
Amonrat Jumnainsong ◽  
Wisitsak Phoksawat ◽  
Wichai Eungpinichpong ◽  
Chanvit Leelayuwat
Keyword(s):  
T Cells ◽  
T Cell ◽  
Crossover Study ◽  
Intracellular Cytokine Staining ◽  
The Elderly ◽  
Complementary Therapy ◽  
T Cell Subsets ◽  
Cd4 T Cell ◽  
T Subsets ◽  
Randomized Crossover Study

The beneficial physiological effects of traditional Thai massage (TTM) have been previously documented. However, its effect on immune status, particularly in the elderly, has not been explored. This study aimed to investigate the effects of multiple rounds of TTM on senescent CD4+ T cell subsets in the elderly. The study recruited 12 volunteers (61–75 years), with senescent CD4+ T cell subsets, who received six weekly 1-h TTM sessions or rest, using a randomized controlled crossover study with a 30-day washout period. Flow cytometry analysis of surface markers and intracellular cytokine staining was performed. TTM could attenuate the senescent CD4+ T cell subsets, especially in CD4+28null NKG2D+ T cells (n = 12; p < 0.001). The participants were allocated into two groups (low < 2.75% or high ≥ 2.75%) depending on the number of CD4+28null NKG2D+ T cells. After receiving TTM over 6 sessions, the cell population of the high group had significantly decreased (p < 0.001), but the low group had no significant changes. In conclusion, multiple rounds of TTM may promote immunity through the attenuation of aberrant CD4+ T subsets. TTM may be provided as a complementary therapy to improve the immune system in elderly populations.

scholarly journals Detection of IFNγ-Secreting CD4+ and CD8+ Memory T Cells in COVID-19 Convalescents after Stimulation of Peripheral Blood Mononuclear Cells with Live SARS-CoV-2

Viruses ◽  
2021 ◽  
Vol 13 (8) ◽  
pp. 1490
Author(s):  
Victoria Matyushenko ◽  
Irina Isakova-Sivak ◽  
Igor Kudryavtsev ◽  
Arina Goshina ◽  
Anna Chistyakova ◽  
...  
Keyword(s):  
T Cells ◽  
T Cell ◽  
Memory T Cells ◽  
Natural Infection ◽  
Intracellular Cytokine Staining ◽  
T Cell Responses ◽  
Effector Memory ◽  
Memory T Cell ◽  
Cell Responses ◽  
Stimulation Of

Background: New coronavirus SARS-CoV-2, a causative agent of the COVID-19 pandemic, has been circulating among humans since November 2019. Multiple studies have assessed the qualitative and quantitative characteristics of virus-specific immunity in COVID-19 convalescents, however, some aspects of the development of memory T-cell responses after natural SARS-CoV-2 infection remain uncovered. Methods: In most of published studies T-cell immunity to the new coronavirus is assessed using peptides corresponding to SARS-CoV-1 or SARS-CoV-2 T-cell epitopes, or with peptide pools covering various parts of the viral proteins. Here, we determined the level of CD4+ and CD8+ memory T-cell responses in COVID-19 convalescents by stimulating PBMCs collected 1 to 6 months after recovery with sucrose gradient-purified live SARS-CoV-2. IFNγ production by the central and effector memory helper and cytotoxic T cells was assessed by intracellular cytokine staining assay and flow cytometry. Results: Stimulation of PBMCs with live SARS-CoV-2 revealed IFNγ-producing T-helper effector memory cells with CD4+CD45RA−CCR7− phenotype, which persisted in circulation for up to 6 month after COVID-19. In contrast, SARS-CoV-2-specific IFNγ-secreting cytotoxic effector memory T cells were found at significant levels only shortly after the disease, but rapidly decreased over time. Conclusion: The stimulation of immune cells with live SARS-CoV-2 revealed a rapid decline in the pool of effector memory CD8+, but not CD4+, T cells after recovery from COVID-19. These data provide additional information on the development and persistence of cellular immune responses after natural infection, and can inform further development of T cell-based SARS-CoV-2 vaccines.

scholarly journals Innate Immune Cells and Their Contribution to T-Cell-Based Immunotherapy

2020 ◽  
Vol 21 (12) ◽  
pp. 4441 ◽  
Author(s):  
Pierpaolo Ginefra ◽  
Girieca Lorusso ◽  
Nicola Vannini
Keyword(s):  
T Cells ◽  
T Cell ◽  
Cancer Immunotherapy ◽  
Cancer Patients ◽  
Immune Cells ◽  
Adoptive Cell Therapy ◽  
Adaptive Immune Response ◽  
Immune Checkpoint Blockade ◽  
Innate Immune ◽  
Innate Immune Cells

In recent years, immunotherapy has become the most promising therapy for a variety of cancer types. The development of immune checkpoint blockade (ICB) therapies, the adoptive transfer of tumor-specific T cells (adoptive cell therapy (ACT)) or the generation of T cells engineered with chimeric antigen receptors (CAR) have been successfully applied to elicit durable immunological responses in cancer patients. However, not all the patients respond to these therapies, leaving a consistent gap of therapeutic improvement that still needs to be filled. The innate immune components of the tumor microenvironment play a pivotal role in the activation and modulation of the adaptive immune response against the tumor. Indeed, several efforts are made to develop strategies aimed to harness innate immune cells in the context of cancer immunotherapy. In this review, we describe the contribution of innate immune cells in T-cell-based cancer immunotherapy and the therapeutic approaches implemented to broaden the efficacy of these therapies in cancer patients.

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