Challenges and future perspectives of T cell immunotherapy in cancer

Abstract

Since the formulation of the tumour immunosurveillance theory, considerable focus has been on enhancing the effectiveness of host antitumour immunity, particularly with respect to T cells. A cancer evades or alters the host immune response by various ways to ensure its development and survival. These include modifications of the immune cell metabolism and T cell signaling. An inhibitory cytokine milieu in the tumour microenvironment also leads to immune suppression and tumour progression within a host. This review traces the development in the field and attempts to summarize the hurdles that the approach of adoptive T cell immunotherapy against cancer faces, and discusses the conditions that must be improved to allow effective eradication of cancer.

ΔPK oncolytic activity includes modulation of the tumour cell milieu

“…The immunosuppressive tumour microenvironment contributes to the relatively poor clinical efficacy of OV treatment (de Aquino et al, 2015), but the contribution of direct melanoma cell secretion of immunosuppressive cytokines is still poorly understood. Our studies focused on the immunosuppressive cytokine IL-10 and multiple inflammatory cytokines (TNF-a, IL1b, GM-CSF).…”

Induction of tumor regression by intratumoral STING agonists combined with anti–programmed death‐L1 blocking antibody in a preclinical squamous cell carcinoma model

“…2,3 Monoclonal antibodies targeting cytotoxic T-lymphocyte-associated protein 4 and programmed death pathways, so-called checkpoint inhibitors, are currently Food and Drug Administration approved for the treatment of advanced melanoma, 4 and a variety of other monoclonal antibodies, cancer vaccines, and immunologically active molecules are under investigation for use in cancer therapy. 2,[5][6][7][8] Cyclic dinucleotides (CDNs) are bacterial intracellular messengers that can activate immune-mediated signaling cascades in eukaryotic cells. 9 CDNs bind and activate stimulator of interferon genes (STING), a cytosolic receptor in eukaryotic cells, which leads to STING-dependent activation of TBK-1-IRF-3 signaling and type I interferon expression.…”

Adoptive T cell therapy: An overview of obstacles and opportunities

“…T cells home to a target site using chemokine receptors. However, tumor and myeloid cells at the TME tend to alter chemokine expression to impair T cell trafficking into the tumor site . We previously reported that melanoma cells abundantly express and secrete the chemokines CXCL1 and CXCL8, which contribute to inflammation and angiogenesis but not to T cell recruitment, as the relevant chemokine receptors are rarely expressed by antimelanoma T cells .…”