Weekly Digests

2021

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AACR Annual Meeting 2021

April 21, 2021

Last week, the ACIR team attended the virtual AACR Annual Meeting 2021. This week’s extensive special feature covers select talks from the conference. We have organized the content by topics below. Tumor microenvironment and effective immunotherapySergio QuezadaTheresa KolbenAntoni RibasIra Mellman Combination therapiesTaha MerghoubGeorge Coukos T cell dysfunction and exhaustionE. John WherryAndrea SchietingerDaniela Stefanie...

DCs can TAP out of ordinary cross-presentation

April 14, 2021

Our classic understanding of antigen presentation to CD8+ T cells involves transport of cytosolic peptides into the endoplasmic reticulum (ER) by the transporter associated with antigen processing (TAP), where they can be loaded onto MHC class I molecules through the canonical peptide loading complex. Cross-presentation occurs when extracellular antigens are presented on MHC-I...

Lymphangiogenesis gets vaccine responses back on track

April 7, 2021

Lymphangiogenesis, the growth of lymphatic vessels, has contradictory consequences in cancer; within the tumor, it is associated with metastasis and poor prognosis, but outside of the tumor, it can boost T cell immunity. Using this knowledge, Sasso et al. developed a cancer vaccine strategy to increase tumor control and immune memory. The preclinical...

How do we improve DC vaccines? Let us count the ways.

March 31, 2021

In previous arms of a sequential, multi-arm, ovarian cancer clinical trial, Tanyi and Chiang et al. showed that the use of a dendritic cell vaccine consisting of DCs pulsed with oxidized autologous whole tumor lysate (OCDC) can elicit T cell responses to tumor-associated antigens and neoantigens. They also showed that the addition of Bevacizumab...

TIL going viral: detection of TCR cross-specificity for viral and tumor antigens

March 24, 2021

Virus-specific tumor-infiltrating T cells have previously been considered bystander cells not contributing to the antitumor response in the same way that T cells specific to tumor-associated antigens (TAAs) might. To begin to unpack the vast amount of TCR sequence data available from tumor and normal tissue samples, Chiou and Tseng et al. used...

T cells and myeloid cells may be in a “dysfunctional” friendship

March 17, 2021

The role of the tumor immune microenvironment (TME) in tumor progression is increasingly appreciated, but for certain cancers, our understanding remains incomplete. Recently, single-cell analysis techniques have enabled comprehensive analysis and supported our knowledge of tumor development and treatment response. Now published in Cancer Cell, Braun and Street et al. used single-cell RNA...

Defining CD4+ T cells with a license to kill

March 10, 2021

The helper function of CD4+ T cells in antitumor immune responses has been characterized, but much less is known about the role of cytotoxic CD4+ Th cells (Th-CTX) in tumors. Cachot, Bilous, and Liu et al. investigated the presence, phenotype, and cytolytic function of tumor-specific Th-CTX using single-cell transcriptomics, peptide–MHC-II multimers, and a...

Epitope spreading is spreading success in immunotherapy

March 3, 2021

Successful immune checkpoint blockade in patients with melanoma is often associated with a high mutational burden, a high level of predicted neoantigens, and an interesting side effect – vitiligo. In a study recently published in Science Translational Medicine, Lo et al. investigated whether vitiligo, an autoimmune reaction against melanocytes, contributes to the efficacy...

Tumors don’t want an invite to the TCR-T cell party

February 24, 2021

Given that it is consistently expressed by tumor cells and contributes to malignant transformation, the HPV E7 antigen is an interesting target for immunotherapy in HPV-associated carcinomas. Nagarsheth et al. previously developed a high avidity TCR that recognizes the E711-19 antigen complexed with HLA-A*02:01. The TCR-T cells containing this E7-targeting TCR were assessed...

Trust a first responder’s gut

February 17, 2021

A growing understanding of the gut microbiome has uncovered critical roles in regulating host immunity, metabolic health, and progression of diseases such as cancer. Recently, the composition of the microbiome has been linked to anti-PD-1 therapeutic response. Fecal microbiota transplant (FMT), in which favorable bacterial species (in this case, those conducive to anti-PD-...

Multiple routes lead to Rome: new insights in TIL origins

February 10, 2021

Even though TILs predict survival and response to immune checkpoint inhibition in non-small cell lung cancer (NSCLC), the origins of these cells remain largely unknown. Gueguen and Metoikidou et al. performed single-cell RNAseq (scRNAseq) and TCRseq (scTCRseq) on tumors, healthy adjacent tissue (juxtatumor), and peripheral blood to investigate CD8+ TIL differentiation and origin...

NeoVax: A Long-Term Follow-up

February 3, 2021

“Durable immunity is a hallmark of successful vaccination,” according to Hu, Leet, and Allesøe et al. in a paper published in Nature Medicine. The team of researchers recently followed up on the long-term effects of vaccination with NeoVax, a long-peptide vaccine that targets up to 20 personal neoantigens per patient. Their recent data extends...

Checkpoint receptors - unexpectedly essential for forming memory T cells

January 27, 2021

Even though the importance of forming long-lived memory CD8+ T cells is widely acknowledged, the origin of this T cell subset remains largely unknown. Johnnidis and Muroyama et al. used a well established viral infection model to phenotype and functionally characterize the cell subsets responsible for memory formation and recall responses, and uncovered...

Make it a double: bispecific antibodies targeting PD-1 and CTLA-4

January 20, 2021

Dual blockade of PD-1 and CTLA-4 checkpoint molecules using monoclonal antibodies has taken advantage of their distinct and complementary mechanisms to enhance clinical responses over monotherapies. However, many patients still fail to respond, and over half of patients experience severe treatment-related adverse events. To improve upon these outcomes, researchers have investigated bispecific targeting...

Focus on suppressive macrophages may boost effects of PARP inhibitors

January 13, 2021

Even though FDA-approved poly(ADP-ribose) polymerase inhibition (PARPi) can be very effective in BRCA-mutant breast cancer, responses are not durable, prompting a need for combination therapies. To provide a mechanistic basis for considering immunotherapeutic strategies, Mehta et al. used high-dimensional single-cell and multi-omics profiling in patient samples and in mouse models to study changes...

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