Addressing current challenges and future directions in immuno-oncology: expert perspectives from the 2017 NIBIT Foundation Think Tank, Siena, Italy

Maio, Michele; Coukos, George; Ferrone, Soldano; Fox, Bernard A.; Fridman, Wolf‐Herman; Garcia, Patrick L.; Lahn, Michael; Provendier, O; Russo, Vincenzo; Rüttinger, Dominik; Shalabi, Aiman; Trajanoski, Zlatko; Viallet, Jean; Wolchok, Jedd D.; Ibrahim, Ramy

doi:10.1007/s00262-018-2285-y

Cited by 8 publications

(3 citation statements)

References 46 publications

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“…The annual Think Tank meeting of the Italian Network for Tumor Biotherapy (NIBIT) Foundation is a forum of experts where current and future developments in basic and clinical research of immuno-oncology (IO) therapies are being discussed [1,2]. In recent years, the IO experts of the Think Tank focused on understanding why certain tumor types responded to immune checkpoint inhibitors (ICI) while others fail to respond to such immune therapies.…”

Section: Introductionmentioning

confidence: 99%

A vision of immuno-oncology: the Siena think tank of the Italian network for tumor biotherapy (NIBIT) foundation

Maio

Lahn²,

Giacomo

et al. 2021

J Exp Clin Cancer Res

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Background The yearly Think Tank Meeting of the Italian Network for Tumor Biotherapy (NIBIT) Foundation, brings together in Siena, Tuscany (Italy), experts in immuno-oncology to review the learnings from current immunotherapy treatments, and to propose new pre-clinical and clinical investigations in selected research areas. Main While immunotherapies in non-small cell lung cancer and melanoma led to practice changing therapies, the same therapies had only modest benefit for patients with other malignancies, such as mesothelioma and glioblastoma. One way to improve on current immunotherapies is to alter the sequence of each combination agent. Matching the immunotherapy to the host’s immune response may thus improve the activity of the current treatments. A second approach is to combine current immunotherapies with novel agents targeting complementary mechanisms. Identifying the appropriate novel agents may require different approaches than the traditional laboratory-based discovery work. For example, artificial intelligence-based research may help focusing the search for innovative and most promising combination partners. Conclusion Novel immunotherapies are needed in cancer patients with resistance to or relapse after current immunotherapeutic drugs. Such new treatments may include targeted agents or monoclonal antibodies to overcome the immune-suppressive tumor microenvironment. The mode of combining the novel treatments, including vaccines, needs to be matched to the patient’s immune status for achieving the maximum benefit. In this scenario, specific attention should be also paid nowadays to the immune intersection between COVID-19 and cancer.

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Section: Introductionmentioning

confidence: 99%

A vision of immuno-oncology: the Siena think tank of the Italian network for tumor biotherapy (NIBIT) foundation

Maio

Lahn²,

Giacomo

et al. 2021

J Exp Clin Cancer Res

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“…The remainder of patients experiences little to no beneficial health outcomes 2,3 . Numerous potential pathways have been identified that should produce a synergistic effect with PD-1 inhibition 4,5 . The lymphocyte-activation gene 3 (LAG3) receptor facilitates an additional checkpoint pathway, and is commonly coexpressed with PD1 on T cells, and presents a major target of interest for combination therapy 3,[6][7][8][9][10] .…”

Section: Introductionmentioning

confidence: 99%

Quantifying the efficacy of checkpoint inhibitors on CD8+ cytotoxic T cells for immunotherapeutic applications via single-cell interaction

et al. 2020

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The inhibition of the PD1/PDL1 pathway has led to remarkable clinical success for cancer treatment in some patients. Many, however, exhibit little to no response to this treatment. To increase the efficacy of PD1 inhibition, additional checkpoint inhibitors are being explored as combination therapy options. TSR-042 and TSR-033 are novel antibodies for the inhibition of the PD1 and LAG3 pathways, respectively, and are intended for combination therapy. Here, we explore the effect on cellular interactions of TSR-042 and TSR-033 alone and in combination at the single-cell level. Utilizing our droplet microfluidic platform, we use time-lapse microscopy to observe the effects of these antibodies on calcium flux in CD8+ T cells upon antigen presentation, as well as their effect on the cytotoxic potential of CD8+ T cells on human breast cancer cells. This platform allowed us to investigate the interactions between these treatments and their impacts on T-cell activity in greater detail than previously applied in vitro tests. The novel parameters we were able to observe included effects on the exact time to target cell killing, contact times, and potential for serial-killing by CD8+ T cells. We found that inhibition of LAG3 with TSR-033 resulted in a significant increase in calcium fluctuations of CD8+ T cells in contact with dendritic cells. We also found that the combination of TSR-042 and TSR-033 appears to synergistically increase tumor cell killing and the single-cell level. This study provides a novel single-cell-based assessment of the impact these checkpoint inhibitors have on cellular interactions with CD8+ T cells.

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“…Numerous potential pathways have been identified that should produce a synergistic effect with PD-1 inhibition (118,119). The lymphocyte-activation gene 3 (LAG3) receptor facilitates an additional checkpoint pathway, and is commonly co-expressed with PD1 on T cells (120).…”

Section: Overviewmentioning

confidence: 99%

Development of integrated platform of lymphocyte phenotyping, and immunotherapy validation in single cell and 3D droplet microfluidic systems

Sullivan

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Addressing current challenges and future directions in immuno-oncology: expert perspectives from the 2017 NIBIT Foundation Think Tank, Siena, Italy

Cited by 8 publications

References 46 publications

A vision of immuno-oncology: the Siena think tank of the Italian network for tumor biotherapy (NIBIT) foundation

A vision of immuno-oncology: the Siena think tank of the Italian network for tumor biotherapy (NIBIT) foundation

Quantifying the efficacy of checkpoint inhibitors on CD8+ cytotoxic T cells for immunotherapeutic applications via single-cell interaction

Development of integrated platform of lymphocyte phenotyping, and immunotherapy validation in single cell and 3D droplet microfluidic systems

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