P33.19 Association Between Expression of Immune Response-Related Genes and Response to Nivolumab in Metastatic Non-Small Cell Lung Cancer

The binding of programmed death ligand-1 and ligand-2 (PD-L1 and PD-L2) to PD-1 blocks T-cell–mediated immune response to tumor. Antibodies that target programmed death receptor-1 (PD-1) will block the ligand-receptor interface, thereby allowing T cells to attack the tumor and increase antitumor immune response. In clinical trials, PD-1 inhibitors have been associated with an approximately 20% overall response rate in unselected patients with non–small cell lung cancer, with sustained tumor response in a subset of patients treated by these immune checkpoint inhibitors. Facing a proliferation of PD-L1 immunohistochemistry clones, staining platforms, and scoring criteria, the pathologist must decide on the feasibility of introducing a newly approved companion diagnostic assay that may require purchase not only of a specific antibody kit but of a particular staining platform. Given the likely reality that clinical practice may, in the near future, demand access to 4 different PD-L1 antibodies coupled with different immunohistochemistry platforms, laboratories will be challenged with deciding among this variety of testing methods, each with its own potential benefits. Another immediate challenge to PD-L1 testing in lung cancer patients is that of access to adequate tumor tissue, given that non–small cell lung cancer samples are often extremely limited in size. With PD-L1 testing it has become clear that the historically used US regulatory approach of one assay–one drug will not be sustainable. One evolving concept is that of complementary diagnostics, a novel regulatory pathway initiated by the US Food and Drug Administration, which is distinct from companion diagnostics in that it may present additional flexibility. Although pathologists need to face the practical reality that oncologists will be asking regularly for the PD-L1 immunohistochemistry status of their patients' tumors, we should also keep in mind that there may be room for improvement of biomarkers for immunotherapy response. The field is rich with opportunities for investigation into biomarkers of immunotherapy response, particularly in the form of collaborative, multidisciplinary studies that incorporate oncologists, pathologists, and basic scientists. Pathologists must take the lead in the rational incorporation of these biomarkers into clinical practice.

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High number of kinome-mutations in non-small cell lung cancer is associated with reduced immune response and poor relapse-free survival

International Journal of Cancer ◽

10.1002/ijc.30726 ◽

2017 ◽

Vol 141 (1) ◽

pp. 184-190 ◽

Cited By ~ 3

Author(s):

Å. Helland ◽

O. T. Brustugun ◽

S. Nakken ◽

A. R. Halvorsen ◽

T. Dønnem ◽

...

Keyword(s):

Lung Cancer ◽

Immune Response ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung ◽

Relapse Free Survival ◽

Free Survival

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PD-1 and PD-L1 Inhibitors in Advanced Non-small Cell Lung Cancer—Promising Agents and Evolving Questions

Oncology & Hematology Review (US) ◽

10.17925/ohr.2015.11.01.36 ◽

2015 ◽

Vol 11 (01) ◽

pp. 36

Author(s):

Adrian G Sacher ◽

Leena Gandhi ◽

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Keyword(s):

Lung Cancer ◽

Immune Response ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Checkpoint Inhibitors ◽

Small Cell ◽

Immune Checkpoints ◽

Clinical Activity ◽

Small Cell Lung ◽

The Impact

There exists increasing evidence that PD-1 and PD-L1 inhibitors may be effective in the treatment of non-small cell lung cancer (NSCLC) an unforeseen finding given the early failure of several immuno- and vaccine-based therapies in this field. This suggests that NSCLC is a more immunogenic tumor than initially appreciated and that it may manipulate various immune checkpoints in order to blunt a potential anti-tumor immune response. NSCLC has subsequently been shown to commonly overexpress PD-L1 as a means of suppressing such cell-mediated immune response through PD-1-mediated signaling. Numerous PD-1 and PD-L1 inhibitors are currently in development as well as various combinations of these inhibitors with chemotherapy, kinase inhibitors, and other immune checkpoint inhibitors. Although these treatments have demonstrated clinical activity in early phase clinical trials, reliable data on the impact of these agents on clinically meaningful endpoints in advanced NSCLC remains scarce. Important questions remain unanswered regarding the appropriate use of PD-L1 expression as a predictive biomarker for the use of these agents as well as the ability of the aforementioned drug combinations to achieve durable disease control.

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Immune response induced in small-cell lung cancer by maintenance therapy with interferon gamma

Lung Cancer ◽

10.1016/0169-5002(94)90340-9 ◽

1994 ◽

Vol 11 (1-2) ◽

pp. 134

Keyword(s):

Lung Cancer ◽

Immune Response ◽

Maintenance Therapy ◽

Small Cell Lung Cancer ◽

Interferon Gamma ◽

Cell Lung Cancer ◽

Small Cell ◽

Small Cell Lung

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Prognostic significance of peripheral blood immune response in early-stage non-small cell lung cancer: a narrative review

AME Medical Journal ◽

10.21037/amj-20-122 ◽

2021 ◽

Vol 0 ◽

pp. 0-0

Author(s):

Sainath Asokan ◽

Anthony Y. Cheung ◽

Flaminio Pavesi ◽

Ashank Bains

Keyword(s):

Lung Cancer ◽

Immune Response ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Peripheral Blood ◽

Early Stage ◽

Prognostic Significance ◽

Small Cell ◽

Narrative Review ◽

Small Cell Lung

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Allogeneic Vaccination With a B7.1 HLA-A Gene-Modified Adenocarcinoma Cell Line in Patients With Advanced Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2004.10.197 ◽

2004 ◽

Vol 22 (14) ◽

pp. 2800-2807 ◽

Cited By ~ 76

Author(s):

Luis E. Raez ◽

Peter A. Cassileth ◽

James J. Schlesselman ◽

Kasi Sridhar ◽

Swaminathan Padmanabhan ◽

...

Keyword(s):

Lung Cancer ◽

Immune Response ◽

Partial Response ◽

Small Cell Lung Cancer ◽

Cell Lung Cancer ◽

Stable Disease ◽

Tumor Vaccine ◽

Small Cell ◽

Good Survival ◽

Small Cell Lung

Purpose To determine the safety, immunogenicity, and clinical response to an allogeneic tumor vaccine for non–small-cell lung cancer, we conducted a phase I trial in patients with advanced metastatic disease. Patients and Methods We treated 19 patients with a vaccine based on an adenocarcinoma line (AD100) transfected with B7.1 (CD80) and HLA A1 or A2. Patients were vaccinated intradermally with 5 × 107 cells once every 2 weeks. Three vaccinations represented one course of treatment. If patients had complete response, partial response, or stable disease, they continued with the vaccinations for up to three courses (nine vaccinations). Immune response was assessed by a change between pre-study and postvaccination enzyme-linked immunospot frequency of purified CD8 T-cells secreting interferon-gamma in response to in vitro challenge with AD100. Results Four patients experienced serious adverse events that were unrelated to vaccine. Another four patients experienced only minimal skin erythema. All but one patient had a measurable CD8 response after three immunizations. The immune response of six surviving, clinically responding patients shows that CD8 titers continue to be elevated up to 150 weeks, even after cessation of vaccination. Overall, one patient had a partial response, and five had stable disease. Median survival for all patients is 18 months (90% CI, 7 to 23 months), with corresponding estimates of 1-year, 2-year, and 3-year survival of 52%, 30%, and 30%, respectively. HLA matching of vaccine, age, sex, race, and pathology did not bear a significant relation to response. Conclusion Minimal toxicity and good survival in this small population suggest clinical benefit from vaccination.

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Induction of Immune Responses and Clinical Efficacy in a Phase II Trial of IDM-2101, a 10-Epitope Cytotoxic T-Lymphocyte Vaccine, in Metastatic Non–Small-Cell Lung Cancer

Journal of Clinical Oncology ◽

10.1200/jco.2008.16.6462 ◽

2008 ◽

Vol 26 (27) ◽

pp. 4418-4425 ◽

Cited By ~ 65

Author(s):

Minal Barve ◽

James Bender ◽

Neil Senzer ◽

Casey Cunningham ◽

F. Anthony Greco ◽

...

Keyword(s):

Lung Cancer ◽

Immune Response ◽

Small Cell Lung Cancer ◽

Clinical Efficacy ◽

T Lymphocyte ◽

Cell Lung Cancer ◽

Cytotoxic T Lymphocyte ◽

Small Cell ◽

Low Grade ◽

Small Cell Lung

Purpose Generation of broad cytotoxic T-lymphocyte responses against multiple epitopes and tumor-associated antigens (TAAs) may provide effective immunotherapy in patients with cancer. We evaluated a single-vial peptide vaccine consisting of nine HLA-A2 supertype-binding epitopes (two native and seven analog epitopes modified for optimal HLA binding or T-cell receptor stimulation) covering five TAAs and the universal helper pan-DR epitope, formulated as a stable emulsion with incomplete Freund's adjuvant (Montanide ISA 51; Seppic SA, Paris, France). The clinical efficacy, safety, and multiepitope immunogenicity of IDM-2101 was evaluated in patients with stage IIIB or IV non–small-cell lung cancer (NSCLC). Patients and Methods A total of 63 patients were enrolled who were positive for HLA-A2. End points included survival, safety, and immune response. IDM-2101 (previously EP-2101) was administered every 3 weeks for the first 15 weeks, then every 2 months through year 1, then quarterly through year 2, for a total of 13 doses. Epitope-specific cytotoxic and helper T-lymphocyte immunogenic responses were measured by the interferon gamma enzyme-linked immunosorbent spot assay. Results No significant adverse events were noted. Low-grade erythema and pain at the injection site were the most common adverse effects. One-year survival in the treated patients was 60%, and median survival was 17.3 months. One complete and one partial response were identified. Survival was longer in patients demonstrating an immune response to epitope peptides (P < .001). Conclusion IDM-2101 was well tolerated, and evidence of efficacy was suggested.

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