CD8+ T cells and NK cells: parallel and complementary soldiers of immunotherapy

Rosenberg, Jillian; Huang, Jun

doi:10.1016/j.coche.2017.11.006

Cited by 129 publications

(100 citation statements)

References 150 publications

(133 reference statements)

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“…Here, we found that a high level of CD8+ T cells was associated with prolonged OS in KICH and that a high level of resting memory CD4+ T cells was associated with a better outcome in KIRC. Regarding subpopulations of T cells, CD8+ T cells are critical anti–tumor effector cells, while resting memory CD4+ T cells can differentiate further to possess various functions (eg, differentiate to CD8 + memory T cells to suppress tumor growth) . We observed a lower fraction of CD8+ T cells in KICH compared with KIRC and KIRP, suggesting that KICH might have an immune‐excluded phenotype where CD8+ T cells were maintained in the stroma, restricting cancer immunity.…”

Section: Discussionmentioning

confidence: 78%

“…T cells are critical anti-tumor effector cells, while resting memory CD4+ T cells can differentiate further to possess various functions (eg, differentiate to CD8 + memory T cells to suppress tumor growth). 31,32 We observed a lower fraction of CD8+ T cells in KICH compared with KIRC and KIRP, suggesting that KICH might have an immune-excluded phenotype where CD8+ T cells were maintained in the stroma, restricting cancer immunity. Interestingly, the infiltration of cytotoxic CD8+ T cells might be modified by immunotherapy.…”

Section: Discussionmentioning

confidence: 82%

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Immune infiltration in renal cell carcinoma

et al. 2019

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Immune infiltration of tumors is closely associated with clinical outcome in renal cell carcinoma ( RCC ). Tumor‐infiltrating immune cells ( TIIC s) regulate cancer progression and are appealing therapeutic targets. The purpose of this study was to determine the composition of TIIC s in RCC and further reveal the independent prognostic values of TIIC s. CIBERSORT , an established algorithm, was applied to estimate the proportions of 22 immune cell types based on gene expression profiles of 891 tumors. Cox regression was used to evaluate the association of TIIC s and immune checkpoint modulators with overall survival ( OS ). We found that CD 8+ T cells were associated with prolonged OS (hazard ratio [ HR ] = 0.09, 95% confidence interval [ CI ].01‐.53; P = 0.03) in chromophobe carcinoma ( KICH ). A higher proportion of regulatory T cells was associated with a worse outcome ( HR = 1.59, 95% CI 1.23‐.06; P < 0.01) in renal clear cell carcinoma ( KIRC ). In renal papillary cell carcinoma ( KIRP ), M1 macrophages were associated with a favorable outcome ( HR = .43, 95% CI .25‐.72; P < 0.01), while M2 macrophages indicated a worse outcome ( HR = 2.55, 95% CI 1.45‐4.47; P < 0.01). Moreover, the immunomodulator molecules CTLA 4 and LAG 3 were associated with a poor prognosis in KIRC , and IDO 1 and PD ‐L2 were associated with a poor prognosis in KIRP . This study indicates TIIC s are important determinants of prognosis in RCC meanwhile reveals potential targets and biomarkers for immunotherapy development.

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Section: Discussionmentioning

confidence: 78%

Section: Discussionmentioning

confidence: 82%

Immune infiltration in renal cell carcinoma

et al. 2019

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“…Moreover, CD4 memory resting T cells as a single TIICs subset occupied the biggest proportion (24%). As a subpopulation of T cells, CD4 memory resting T cells could further differentiation and been given a various function, including aid CD8 + T cells in tumor rejection, suppressing harmful immunological reactions to self‐ and foreign antigens and even blocking CD8 + T‐cell activation and NK cell killing . Thus, it can be seen that CD4 memory resting T cells play a pivotal role in the development of CRC and its direction of differentiation could be a potential therapeutic target.…”

Section: Discussionmentioning

confidence: 99%

Profiles of immune infiltration in colorectal cancer and their clinical significant: A gene expression‐based study

et al. 2018

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Immune infiltration of colorectal cancer (CRC) is closely associated with clinical outcome. However, previous work has not accounted for the diversity of functionally distinct cell types that make up the immune response. In this study, based on a deconvolution algorithm (known as CIBERSORT) and clinical annotated expression profiles, we comprehensively analyzed the tumor‐infiltrating immune cells present in CRC for the first time. The fraction of 22 immune cells subpopulations was evaluated to determine the associations between each cell type and survival and response to chemotherapy. As a result, profiles of immune infiltration vary significantly between paired cancer and paracancerous tissue and the variation could characterize the individual differences. Of the cell subpopulations investigated, tumors lacking M1 macrophages or with an increased number of M2 macrophages, eosinophils, and neutrophils were associated with the poor prognosis. Unsupervised clustering analysis using immune cell proportions revealed five subgroups of tumors, largely defined by the balance between macrophages M1, M2, and NK resting cells, with distinct survival patterns, and associated with well‐established molecular subtype. Collectively, our data suggest that subtle differences in the cellular composition of the immune infiltrate in CRC appear to exist, and these differences are likely to be important determinants of both prognosis and response to treatment.

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“…Macrophages are mainly classi ed into M0/M1/M2 Under speci c conditions, M0 macrophages can be polarized to M1/M2 types, Liu et al 28 found that RhoA pathway could obstruct elongation (hummingbird phenotype) of M0 macrophages, suggesting that M0 may be important in bone-marrow-derived macrophages. As subpopulations of T cells, resting memory CD4+ T cells can differentiate to perform other functions (separate to those mediated by memory CD8 + T cells, but aiding in suppressing growth of tumors) [29][30] .…”

Section: Discussionmentioning

confidence: 99%

Characterization of tumor microenvironment and Immune infiltration in head and neck squamous cell carcinoma

cheng²

2020

Preprint

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Background: Head and neck squamous cell carcinoma (HNSCC), is a frequent malignant tumor of the head and neck. Most HNSCC arise in the lip, oral cavity, paranasal sinuses, oropharynx, larynx, nasopharynx, and the pharynx. HNSCC is a heterogeneous disease entity, and the role of immune cells in HNSCC, particularly in immunotherapy has not yet been extensively studied. Method: In this study, we applied CIBERSORT to infer the infiltration of 22 subsets of TIICs using gene expression data. This was to determine the relationship of the immune subpopulation, patients’ survival, function, and expression differences to reveal potential targets and biomarkers for immunotherapy. Results: Somatic mutations were the most common and the variant classification was missense mutation. The most common DNA sequence polymorphism type was SNP and the most common single nucleotide variants (SNV) class was C>T. The median number of variants per sample was 78 in HNSCC patients. The top 10 mutated genes related to TMB were TP53, TTN, FAT1, MUC16, CDKN2A, CSMD3, SYNE1, LRP1B, NOTCH1, and PIK3CA. We portrayed the immune scene in detail, uncovering the awesome immune infiltration styles of various subtypes in HNSCC. Conclusion: The intricate connection between TIIC, TMB, and genomic alterations was additionally set up. Our paintings advance the information of immune response and offer significant assets for research to enhance immunotherapy.

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CD8+ T cells and NK cells: parallel and complementary soldiers of immunotherapy

Cited by 129 publications

References 150 publications

Immune infiltration in renal cell carcinoma

Immune infiltration in renal cell carcinoma

Profiles of immune infiltration in colorectal cancer and their clinical significant: A gene expression‐based study

Characterization of tumor microenvironment and Immune infiltration in head and neck squamous cell carcinoma

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