Immunological Classification of Tumor Types and Advances in Precision Combination Immunotherapy

Ren, Xiufang; Guo, Songyi; Guan, Xiaojiao; Kang, Yuan; Liu, Jiamei; Yang, Xiaoguang

doi:10.3389/fimmu.2022.790113

Cited by 36 publications

(33 citation statements)

References 71 publications

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Section: Introductionmentioning

confidence: 99%

“…In a similar model that is based on the distribution and number of CD3+ and CD8+ T cells in the center and edge of tumors and also on the expression level of PD-L1, tumors are divided into hot, cold, and intermediate tumors (including immune-suppressed and isolated) ( 160 ). Immune evasion mechanisms in tumor immunology involves factors that inhibit T cells and T cell recruitment, which prevents cytotoxic T cells from entering the TME ( 160 ). In immune-desert tumors, CD8+ T lymphocytes are absent from the tumor and its periphery, while in immune-excluded tumors, CD8+ T cells localize only at invasion margins and do not efficiently penetrate the tumor.…”

Section: Introductionmentioning

confidence: 99%

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Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field

Ashenafi

Brighenti

2022

Front. Immunol.

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Tuberculosis (TB) remains one of the deadliest infectious diseases in the world and every 20 seconds a person dies from TB. An important attribute of human TB is induction of a granulomatous inflammation that creates a dynamic range of local microenvironments in infected organs, where the immune responses may be considerably different compared to the systemic circulation. New and improved technologies for in situ quantification and multimodal imaging of mRNA transcripts and protein expression at the single-cell level have enabled significantly improved insights into the local TB granuloma microenvironment. Here, we review the most recent data on regulation of immunity in the TB granuloma with an enhanced focus on selected in situ studies that enable spatial mapping of immune cell phenotypes and functions. We take advantage of the conceptual framework of the cancer-immunity cycle to speculate how local T cell responses may be enhanced in the granuloma microenvironment at the site of Mycobacterium tuberculosis infection. This includes an exploratory definition of “hot”, immune-inflamed, and “cold”, immune-excluded TB granulomas that does not refer to the level of bacterial replication or metabolic activity, but to the relative infiltration of T cells into the infected lesions. Finally, we reflect on the current knowledge and controversy related to reactivation of active TB in cancer patients treated with immune checkpoint inhibitors such as PD-1/PD-L1 and CTLA-4. An understanding of the underlying mechanisms involved in the induction and maintenance or disruption of immunoregulation in the TB granuloma microenvironment may provide new avenues for host-directed therapies that can support standard antibiotic treatment of persistent TB disease.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field

Ashenafi

Brighenti

2022

Front. Immunol.

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“…In the clinical setting, the difference between the two groups was noted mainly for their responses to immunotherapy, particularly to immune checkpoint inhibitors (ICIs). Malignancies in the hot tumour group have generally shown a better outcome in response to ICIs, such as anti-PD-1, anti-PD-L1, and anti-CTLA-4 drugs; thus, an alternative therapeutic strategy for cold tumours needs to be explored further [ 16 ].…”

Section: Discussionmentioning

confidence: 99%

Regulatory T Cells but Not Tumour-Infiltrating Lymphocytes Correlate with Tumour Invasion Depth in Basal Cell Carcinoma

et al. 2022

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Basal cell carcinoma (BCC) is the most common skin malignancy worldwide. Current evidence suggests tumour-infiltrating lymphocytes (TILs) may influence the clinical outcomes of patients with BCC. The present study aimed to profile the infiltrative characteristics of stromal TILs and regulatory T cells (Treg cells) in the tumour centre (TC), tumour periphery (TP), and normal adjacent tissue (NAT) of BCC. A total of 111 samples from 43 cutaneous BCC cases were examined for TIL (CD3+) and Treg cell (FOXP3+/CD3+) expression using immunohistochemical techniques. The correlations of Treg cells with TILs, invasion depth, and tumour morphological risk were analysed. We identified a high mean proportion of Treg cells within the tumour (TC = 46.9%, TP = 56.1%, NAT = 51.8%) despite a relatively low median of TILs (TC = 12.7%, TP = 10.3%, NAT = 3.6%), supporting the classification of BCC as a cold tumour. A significant positive correlation was observed between the proportion of Treg cells and sTILs (ρ = 0.325, p < 0.001), suggesting a predominant role of TILs in the infiltration of Treg cells. An inverse correlation discovered between Treg cells and tumour invasion depth (r = −0.36, p = 0.017) might indicate Treg cells’ anti-tumour capacity in BCC.

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“…Tumour immune microenvironment can be divided into (i) immunostimulatory or immunologically “hot” and (ii) immunosuppressing or “cold” ( Figure 2 ). The “hot” TME consists of immunostimulating factors and activated immune cells [ 104 ]. Immunostimulating factors include nitric oxide (NO), IL-1β, IL-6, IL-12, TNFα, and IFNs.…”

Section: Tumour Microenvironmentmentioning

confidence: 99%

Recombinant Viral Vectors for Therapeutic Programming of Tumour Microenvironment: Advantages and Limitations

2022

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Viral vectors have been widely investigated as tools for cancer immunotherapy. Although many preclinical studies demonstrate significant virus-mediated tumour inhibition in synergy with immune checkpoint molecules and other drugs, the clinical success of viral vector applications in cancer therapy currently is limited. A number of challenges have to be solved to translate promising vectors to clinics. One of the key elements of successful virus-based cancer immunotherapy is the understanding of the tumour immune state and the development of vectors to modify the immunosuppressive tumour microenvironment (TME). Tumour-associated immune cells, as the main component of TME, support tumour progression through multiple pathways inducing resistance to treatment and promoting cancer cell escape mechanisms. In this review, we consider DNA and RNA virus vectors delivering immunomodulatory genes (cytokines, chemokines, co-stimulatory molecules, antibodies, etc.) and discuss how these viruses break an immunosuppressive cell development and switch TME to an immune-responsive “hot” state. We highlight the advantages and limitations of virus vectors for targeted therapeutic programming of tumour immune cell populations and tumour stroma, and propose future steps to establish viral vectors as a standard, efficient, safe, and non-toxic cancer immunotherapy approach that can complement other promising treatment strategies, e.g., checkpoint inhibitors, CAR-T, and advanced chemotherapeutics.

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Immunological Classification of Tumor Types and Advances in Precision Combination Immunotherapy

Cited by 36 publications

References 71 publications

Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field

Reinventing the human tuberculosis (TB) granuloma: Learning from the cancer field

Regulatory T Cells but Not Tumour-Infiltrating Lymphocytes Correlate with Tumour Invasion Depth in Basal Cell Carcinoma

Recombinant Viral Vectors for Therapeutic Programming of Tumour Microenvironment: Advantages and Limitations

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