CpG-mediated augmentation of CD8+ T-cell responses in mice is attenuated by a water-in-oil emulsion (Montanide ISA-51) but enhanced by an oil-in-water emulsion (IDRI SE)
Adjuvants are a key component in enhancing immunogenicity of vaccines and play a vital role in facilitating the induction of the correct type of immunity required for each vaccine to be optimally efficacious. Several different adjuvants are found in licensed vaccines, and many others are in pre-clinical or clinical testing. Agonists for TLRs are potent activators of the innate immune system and some, such as CpG (TLR9 agonist), are particularly good for promoting cellular immunity because of the induction of Th1 cytokines. Emulsions that have both delivery and adjuvant properties are classified as water-in-oil (W/O) or oil...
Source: International Immunology - August 30, 2016 Category: Allergy & Immunology Authors: Makinen, S. R., Zhu, Q., Davis, H. L., Weeratna, R. D. Tags: Original Research Source Type: research
IL-17A plays a central role in the expression of psoriasis signature genes through the induction of I{kappa}B-{zeta} in keratinocytes
In psoriasis lesions, a diverse mixture of cytokines is up-regulated that influence each other generating a complex inflammatory situation. Although this is the case, the inhibition of IL-17A alone showed unprecedented clinical results in patients, indicating that IL-17A is a critical inducer of psoriasis pathogenesis. To elucidate IL-17A-driven keratinocyte-intrinsic signaling pathways, we treated monolayers of normal human epidermal keratinocytes in vitro with a mixture of six cytokines (IL-17A, TNF-α, IL-17C, IL-22, IL-36 and IFN-) involved in psoriasis to mimic the inflammatory milieu in psoriasis lesions. Microa...
Source: International Immunology - August 30, 2016 Category: Allergy & Immunology Authors: Muromoto, R., Hirao, T., Tawa, K., Hirashima, K., Kon, S., Kitai, Y., Matsuda, T. Tags: featured content Source Type: research
Mycobacterial r32-kDa antigen-specific T-cell responses correlate with successful treatment and a heightened anti-microbial response in human leprosy patients
Conclusions:
These findings suggest that responses to r32-kDa antigen reflect an improved immunological and anti-microbial response in leprosy patients during therapy, thereby indicating its potential use as an immune correlate in the treatment of leprosy patients. (Source: International Immunology)
Source: International Immunology - August 30, 2016 Category: Allergy & Immunology Authors: Neela, V. S. K., Devalraju, K. P., Pydi, S. S., Sunder, S. R., Adiraju, K. R., Singh, S. S., Anandaraj, M. P. J. S., Valluri, V. L. Tags: Original Research Source Type: research
Mammary-tumor-educated B cells acquire LAP/TGF-{beta} and PD-L1 expression and suppress anti-tumor immune responses
B lymphocytes play a role in inhibiting the immune response against certain tumors, but the underlying mechanisms are poorly understood. EMT-6 mammary tumors grow well in wild-type (WT) mice but show reduced growth in B-cell-deficient μ–/– BALB/c mice (BCDM). WT mice demonstrate extensive B-cell infiltration into the tumor bed, reduced CD8+ T cell and CD49+ NK cell infiltration, and markedly reduced cytolytic T-cell response relative to BCDM. Expression of LAP/TGF-β1, CD80, CD86 and PD-L1 is significantly increased in tumor-infiltrating B cells (TIL-B) relative to splenic B cells. LAP/TGF-β1 expres...
Source: International Immunology - August 30, 2016 Category: Allergy & Immunology Authors: Zhang, Y., Morgan, R., Chen, C., Cai, Y., Clark, E., Khan, W. N., Shin, S.-U., Cho, H.-M., Al Bayati, A., Pimentel, A., Rosenblatt, J. D. Tags: Original Research Source Type: research
In This Issue
(Source: International Immunology)
Source: International Immunology - August 30, 2016 Category: Allergy & Immunology Tags: In This Issue Source Type: research
Table of Contents
(Source: International Immunology)
Source: International Immunology - August 30, 2016 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research
Subscriptions
(Source: International Immunology)
Source: International Immunology - August 30, 2016 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research
Cover
(Source: International Immunology)
Source: International Immunology - August 30, 2016 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research
The role of neoantigens in response to immune checkpoint blockade
Immune checkpoint blockade has demonstrated substantial promise for the treatment of several advanced malignancies. These agents activate the immune system to attack tumor cells. For example, agents targeting CTLA4 and programmed cell death 1 (PD-1) have resulted in impressive response rates and, in some cases, durable remissions. Neoantigens are mutations that encode immunologically active proteins that can cause the immune system to recognize the affected cell as foreign. Recent data have made it clear that these mutations are, in large part, the functional targets of immune checkpoint blockade. This review summarizes th...
Source: International Immunology - July 21, 2016 Category: Allergy & Immunology Authors: Riaz, N., Morris, L., Havel, J. J., Makarov, V., Desrichard, A., Chan, T. A. Tags: Invited review Source Type: research
Roles of regulatory T cells in cancer immunity
CD4+ regulatory T cells (Tregs) expressing the transcription factor FoxP3 are highly immune suppressive and play central roles in the maintenance of self-tolerance and immune homeostasis, yet in malignant tumors they promote tumor progression by suppressing effective antitumor immunity. Indeed, higher infiltration by Tregs is observed in tumor tissues, and their depletion augments antitumor immune responses in animal models. Additionally, increased numbers of Tregs and, in particular, decreased ratios of CD8+ T cells to Tregs among tumor-infiltrating lymphocytes are correlated with poor prognosis in various types of human ...
Source: International Immunology - July 21, 2016 Category: Allergy & Immunology Authors: Takeuchi, Y., Nishikawa, H. Tags: Invited review Source Type: research
Cancer-induced heterogeneous immunosuppressive tumor microenvironments and their personalized modulation
Although recent cancer immunotherapy strategies, including immune-checkpoint blockade (i.e. blocking PD-1, PD-L1 or CTLA-4), have shown durable clinical effects in some (but not all) patients with various advanced cancers, further understanding of human immunopathology, particularly in tumor microenvironments, is essential to improve this type of therapy. The major hurdle for immunotherapy is the immunosuppression that is found in cancer patients. There are two types of immunosuppression: one is induced by gene alterations in cancer; the other is local adaptive immunosuppression, triggered by tumor-specific T cells in tumo...
Source: International Immunology - July 21, 2016 Category: Allergy & Immunology Authors: Yaguchi, T., Kawakami, Y. Tags: Invited review Source Type: research
Mechanisms of tumor escape in the context of the T-cell-inflamed and the non-T-cell-inflamed tumor microenvironment
Checkpoint blockade therapy has been proven to be highly active across many cancer types but emerging evidence indicates that the therapeutic benefit is limited to a subset of patients in each cancer entity. The presence of CD8+ T cells within the tumor microenvironment or the invasive margin of the tumor, as well as the up-regulation of PD-L1, have emerged to be the most predictive biomarkers for clinical benefit in response to checkpoint inhibition. Although the up-regulation of immune inhibitory mechanisms is one mechanism of immune escape, commonly used by T-cell-inflamed tumors, exclusion of an anti-tumor specific T-c...
Source: International Immunology - July 21, 2016 Category: Allergy & Immunology Authors: Spranger, S. Tags: Invited review Source Type: research
Rational bases for the use of the Immunoscore in routine clinical settings as a prognostic and predictive biomarker in cancer patients
The American Joint Committee on Cancer/Union Internationale Contre le Cancer (AJCC/UICC) tumor, nodes, metastasis (TNM) classification system based on tumor features is used for prognosis estimation and treatment recommendations in most cancers. However, the clinical outcome can vary significantly among patients within the same tumor stage and TNM classification does not predict response to therapy. Therefore, many efforts have been focused on the identification of new markers. Multiple tumor cell-based approaches have been proposed but very few have been translated into the clinic. The recent demonstration of the essentia...
Source: International Immunology - July 21, 2016 Category: Allergy & Immunology Authors: Kirilovsky, A., Marliot, F., El Sissy, C., Haicheur, N., Galon, J., Pages, F. Tags: Invited review Source Type: research
Introduction: Cancer Immunology Special Issue--Immunopathology
(Source: International Immunology)
Source: International Immunology - July 21, 2016 Category: Allergy & Immunology Authors: Kawakami, Y. Tags: Introduction Source Type: research
Table of Contents
(Source: International Immunology)
Source: International Immunology - July 21, 2016 Category: Allergy & Immunology Tags: Cover / Standing Material Source Type: research
