Immunotherapies have generated spectacular results in the clinic and changed the treatment scheme for cancer patients with thoracic cancers (1). Recent breakthroughs include checkpoint inhibitors and adoptive cellular therapies.
Immune checkpoint inhibitors, such as anti-PD-1 and anti-CTLA-4 antibodies present a major advance in the treatment of certain thoracic cancers. Since 2015, the US Food and Drug Administration (FDA) has approved a number of anti-PD-1/PD-L1 checkpoint blockade immunotherapies for lung cancers. For example, the anti-PD-1 antibodies Nivolumab and Pembrolizumab, and anti-PD-L1 Atezolizumab and Durvalumab were approved in treating patients with non-small cell lung cancer (NSCLC), and Atezolizumab and Durvalumab recently received FDA approval for treating metastatic small cell lung cancer (SCLC) patients. Anti-CTLA-4 antibody Ipilimumab was approved by FDA in 2011 for the treatment of melanoma and has since undergoing clinical trials for the treatment of different cancers. It was recently reported that Nivolumab plus Ipilimumab was effective and tolerable in treating advanced NSCLC (2). According to this exciting finding, the FDA has granted priority review to the Biologics License Application for this combination therapy for the first-line treatment of patients with metastatic or recurrent NSCLC.
Expansion of tumour-infiltrating T cells or chimeric antigen receptor (CAR) T cells demonstrated great promise in recent years. In early days, tumour infiltrating T cells were isolated and expanded from the tumours and reinfused back to patients for the treatment of melanoma. Although greater than 50% of the patients responded to the treatment (3), this therapy was proved difficult to use in other solid cancers. Subsequently, T cell receptor (TCR) or CAR transduced T cell therapy were developed and tested in the clinic. In particular, CAR T cell therapies have demonstrated their power in certain blood cancers and have received FDA approval for treating these hematologic malignancies. Although both TCR and CAR T cell therapies have only demonstrated moderate effect in solid cancers in the clinic, a number of recent preclinical studies (4-8) and clinical reports (9,10) have shown great promise.
The current challenge for cancer immunotherapies is that although some patients have benefited from the treatments, a number of the patients are resistant. Therefore, there is a strong interest in understanding resistant mechanisms and adopting new therapeutic approaches. One of the major focus in this field is to target the immunosuppressive tumour microenvironment (11,12).
This focused issue aims to provide an in-depth analysis of current literature and future directions for this important clinical topic. The articles collectively comment on the current status of the thoracic cancer treatments, including the treatments to their metastases, the challenges, and some controversial aspects that need to be further investigated in future.
We are grateful for all the contributing authors for their contribution to this special issue and the support from the JTD editorial board.
Provenance and peer review: This article was commissioned by the editorial office, Journal of Thoracic Disease for the series “Immunotherapy and Tumor Microenvironment”. The article did not undergo external peer review.
Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at http://dx.doi.org/10.21037/jtd.2020.03.117). The series “Immunotherapy and Tumor Microenvironment” was commissioned by the editorial office without any funding or sponsorship. PL, CYS and JZ served as the unpaid Guest Editors of the series. The authors have no other conflicts of interest to declare.
Ethical Statement: The authors are accountable for all aspects of the work in ensuring that questions related to the accuracy or integrity of any part of the work are appropriately investigated and resolved.
Open Access Statement: This is an Open Access article distributed in accordance with the Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International License (CC BY-NC-ND 4.0), which permits the non-commercial replication and distribution of the article with the strict proviso that no changes or edits are made and the original work is properly cited (including links to both the formal publication through the relevant DOI and the license). See: https://creativecommons.org/licenses/by-nc-nd/4.0/.
- Kruger S, Ilmer M, Kobold S, et al. Advances in cancer immunotherapy 2019 - latest trends. J Exp Clin Cancer Res 2019;38:268. [Crossref] [PubMed]
- Hellmann MD, Paz-Ares L, Bernabe Caro R, et al. Nivolumab plus Ipilimumab in Advanced Non-Small-Cell Lung Cancer. N Engl J Med 2019;381:2020-31. [Crossref] [PubMed]
- Dudley ME, Wunderlich JR, Yang JC, et al. Adoptive cell transfer therapy following non-myeloablative but lymphodepleting chemotherapy for the treatment of patients with refractory metastatic melanoma. J Clin Oncol 2005;23:2346-57. [Crossref] [PubMed]
- Slaney CY, von Scheidt B, Davenport AJ, et al. Dual-specific Chimeric Antigen Receptor T Cells and an Indirect Vaccine Eradicate a Variety of Large Solid Tumors in an Immunocompetent, Self-antigen Setting. Clin Cancer Res 2017;23:2478-90. [Crossref] [PubMed]
- Westwood JA, Ellis S, Danne J, et al. An ultrastructural investigation of tumors undergoing regression mediated by immunotherapy. Oncotarget 2017;8:115215-29. [Crossref] [PubMed]
- von Scheidt B, Wang M, Oliver AJ, et al. Enterotoxins can support CAR T cells against solid tumors. Proc Natl Acad Sci U S A 2019;116:25229-35. [Crossref] [PubMed]
- Ma L, Dichwalkar T, Chang JYH, et al. Enhanced CAR-T cell activity against solid tumors by vaccine boosting through the chimeric receptor. Science 2019;365:162-8. [PubMed]
- Reinhard K, Rengstl B, Oehm P, et al. An RNA vaccine drives expansion and efficacy of claudin-CAR-T cells against solid tumors. Science 2020;367:446-53. [Crossref] [PubMed]
- Brown CE, Alizadeh D, Starr R, et al. Regression of Glioblastoma after Chimeric Antigen Receptor T-Cell Therapy. N Engl J Med 2016;375:2561-9. [Crossref] [PubMed]
- Zacharakis N, Chinnasamy H, Black M, et al. Immune recognition of somatic mutations leading to complete durable regression in metastatic breast cancer. Nat Med 2018;24:724-30. [Crossref] [PubMed]
- Beavis PA, Slaney CY, Kershaw MH, et al. Reprogramming the tumor microenvironment to enhance adoptive cellular therapy. Semin Immunol 2016;28:64-72. [Crossref] [PubMed]
- Oliver AJ, Davey AS, Keam SP, et al. Tissue-specific tumor microenvironments influence responses to immunotherapies. Clin Transl Immunology 2019;8:e1094. [Crossref] [PubMed]