Immune cell triads reprogram exhausted CD8 T cells for effective tumor elimination.

In this issue of Cancer Cell, Espinosa-Carrasco et al. show that the efficacy of cancer immunotherapies depends upon the formation of intratumoral immune triads between antigen-presenting cells and antigen-specific CD4 and CD8 T cells. This interaction reprograms tumor-specific CD8 T cells to exert potent effector functions and eradicate established solid tumors.

Vaccine Therapy in Non-Small Cell Lung Cancer.

Immunotherapy using immune checkpoint modulators has revolutionized the oncology field, emerging as a new standard of care for multiple indications, including non-small cell lung cancer (NSCLC). However, prognosis for patients with lung cancer is still poor. Although immunotherapy is highly effective in some cases, not all patients experience significant or durable responses, and further strategies are needed to improve outcomes.

Integrin-α-mediated activation of TGF-β regulates anti-tumour CD8 T cell immunity and response to PD-1 blockade.

TGF-β is secreted in the tumour microenvironment in a latent, inactive form bound to latency associated protein and activated by the integrin α subunit. The activation of latent TGF-β by cancer-cell-expressed α re-shapes the tumour microenvironment, and this could affect patient responses to PD-1-targeting therapy. Here we show, using multiplex immunofluorescence staining in cohorts of anti-PD-1 and anti-PD-L1-treated lung cancer patients, that decreased expression of cancer cell α is associated with improved immunotherapy-related, progression-free survival, as well as with an increased density of CD8CD103 tumour-infiltrating lymphocytes.

CD103CD8 T Cells Accumulate in Tumors of Anti-PD-1-Responder Lung Cancer Patients and Are Tumor-Reactive Lymphocytes Enriched with Tc17.

Accumulation of CD103CD8 resident memory T (T) cells in human lung tumors has been associated with a favorable prognosis. However, the contribution of T to anti-tumor immunity and to the response to immune checkpoint blockade has not been clearly established. Using quantitative multiplex immunofluorescence on cohorts of non-small cell lung cancer patients treated with anti-PD-(L)1, we show that an increased density of CD103CD8 lymphocytes in immunotherapy-naive tumors is associated with greatly improved outcomes.

Molecular and Immunological Characterization of Biliary Tract Cancers: A Paradigm Shift Towards a Personalized Medicine.

Biliary tract cancers (BTCs) are a group of rare cancers that account for up to 3-5% of cancer patients worldwide. BTCs include cholangiocarcinoma (CCA), gallbladder cancer (GBC), and ampulla of Vater cancer (AVC). They are frequently diagnosed at an advanced stage when the disease is often found disseminated.

Recent Advances in Lung Cancer Immunotherapy: Input of T-Cell Epitopes Associated With Impaired Peptide Processing.

Recent advances in lung cancer treatment are emerging from new immunotherapies that target T-cell inhibitory receptors, such as programmed cell death-1 (PD-1). However, responses to anti-PD-1 antibodies as single agents are observed in fewer than 20% of non-small-cell lung cancer (NSCLC) patients, and immune mechanisms involved in the response to these therapeutic interventions remain poorly elucidated. Accumulating evidence indicates that effective anti-tumor immunity is associated with the presence of T cells directed toward cancer neoepitopes, a class of major histocompatibility complex (MHC)-bound peptides that arise from tumor-specific mutations.

Resident memory T cells, critical components in tumor immunology.

CD8 T lymphocytes are the major anti-tumor effector cells. Most cancer immunotherapeutic approaches seek to amplify cytotoxic T lymphocytes (CTL) specific to malignant cells. A recently identified subpopulation of memory CD8 T cells, named tissue-resident memory T (T) cells, persists in peripheral tissues and does not recirculate.