What We're Reading
Cancer Immunol Res April 1 2019 7 (4) 527-527;
A patient with metastatic colon cancer had T-cell receptors reactive with a mutation in the tumor suppressor gene TP53. The TCRs were neoantigen-specific and HLA-A*0201-restricted and could be used to treat others with tumors sharing the same parameters.
Mice with altered colon microbiota early in life exhibit augmented inflammatory cytokine and chemokine expression in the colon. This led to an increased susceptibility to colitis-associated cancer later in adulthood, demonstrating the microbiota's impact on colon homeostasis.
This study provides preclinical in vitro and in vivo proof-of-concept for use of Delta One T (DOT) cells as immunotherapy to treat acute myeloid leukemia.
The antitumor activity of anti-CD96 monotherapy depends on several host factors, including CD8+ T cells and immune signaling. Inhibition of CD96 in combination with other immune checkpoint inhibitors shows superior antitumor activity over single or dual agent therapy.
Treatment of murine tumors with combination checkpoint blockade and an antibody-IL2 fusion protein reduces tumor growth, an effect dependent on CD8+ T cells and NK cells. These data support the use of engineered IL2 products for anti-cancer therapy.
Chronic LCMV infection delays tumor progression as a result of sustained type I IFN signaling and enhanced NK cell–mediated immunosurveillance. This observation could improve the development of effective treatment strategies for cancer patients with chronic viral infections.
In a mouse model of B-cell lymphoma, regulatory T cells suppressed antitumor responses. Treg cells recognized nonmutated self epitopes, which were characteristic of lymphoma and which were related to malignancy.
Automated image analysis reveals that high tumor bud numbers, low T-cell density, and few T cells proximal to tumor buds were associated with reduced survival of CRC patients. This model provided greater prognostic value than current clinical guidelines.
Low-dose intravesical administration of Ty21a, a commercial typhoid vaccine, generated effective antitumor DC and T-cell responses and improved survival in a mouse model of bladder cancer. These results demonstrate the potential of Ty21a for clinical use.
Both preclinical and phase IB clinical data indicate that lower-than-conventional doses of the anti-angiogenic agent apatinib (a VEGFR2-TKI) optimized the immunosuppressive tumor microenvironment and potentiated the therapeutic response to anti-PD-1/PD-L1 immunotherapy in lung cancer.
The immune profile of the tumor microenvironment in DLBCL patients was assessed with a MultiOmyx platform. PD-1/L1 expression on T cells and PD-L1 expression on macrophages had prognostic value in identification of patients with poor survival after immunochemotherapy.
Immunotherapy can include vaccines in the setting of autologous stem cell transplantation for multiple myeloma. Here, autologous lymphocyte infusion augmented immunotherapy and supported humoral and CD4+ helper T-cell immunity in response to a therapeutic tumor vaccine.
The response to PD-1 blockade and CD137 agonism could be improved by “re-purposing” radiotherapy or cisplatin to modulate the tumor microenvironment. Chemo/radio-immunotherapy enhances CTL responses, tumor regression, and survival in a mouse model of poorly immunogenic breast cancer.
An engineered T cell specific for two antigens shows anti-AML activity. Combining CD123 recognition and IL7R activation enhances antitumor activity and T-cell survival in preclinical models, suggesting the value of extending this strategy to other tumor types.