Immune Cell Infiltration May Be a Key Determinant of Long-Term Survival in Small Cell Lung Cancer

Prasuna Muppa, Simone Barreto Siqueira Parrilha Terra, Anurag Sharma, Aaron Mansfield, Marie Christine Aubry, Kaustubh Bhinge, Michael K. Asiedu, Mariza De Andrade, Nafiseh Janaki, Stephen J. Murphy, Aqsa Nasir, Virginia Van Keulen, George Vasmatzis, Dennis A Wigle, Ping Yang, Eunhee S. Yi, Tobias D Peikert, Farhad Kosari

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Introduction: Although most patients with SCLC die within a few months of diagnosis, a subgroup of patients survive for many years. Factors determining long-term survivorship remain largely unknown. We present the first comprehensive comparative genomic and tumor microenvironment analyses of SCLC between patients with long-term survivorship and patients with the expected survivorship. Methods: We compared surgically resected tumors of 23 long-term SCLC survivors (survival >4 years) and 18 SCLC survivors with the expected survival time (survival ≤2 years). There were no significant differences in clinical variables, including TNM staging and curative- versus non–curative-intent surgery between the groups. Gene expression profiling was performed by using microarrays, and tumor microenvironment analyses were performed by immunohistochemistry of prominent immune-related markers. Results: Immune-related genes and pathways represented the majority of the differentially overexpressed genes in long-term survivorship compared with in expected survivorship. The differences in the immunological tumor microenvironment were confirmed by quantitative immunostaining. Increased numbers of tumor-infiltrating and associated lymphocytes were present throughout tumors of long-term survivors of SCLC. Several differentiating patterns of enhanced antitumor immunity were identified. Although some areas of the tumors of long-term survivors of SCLC also harbored higher numbers of suppressive immune cells (monocytes, regulatory lymphocytes, and macrophages), the ratios of these suppressive cells to CD3-positive lymphocytes were generally lower in the tumors of long-term survivors of SCLC, indicating a less tumor-suppressive microenvironment. Conclusions: Our data demonstrate that long-term survivorship of patients with SCLC is strongly influenced by the presence of the immune cells in the tumor microenvironment. Characterization of the antitumor immune responses may identify opportunities for individualized immunotherapies for SCLC.

Original languageEnglish (US)
Pages (from-to)1286-1295
Number of pages10
JournalJournal of Thoracic Oncology
Volume14
Issue number7
DOIs
StatePublished - Jul 1 2019

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Small Cell Lung Carcinoma
Tumor Microenvironment
Survival Rate
Survivors
Survival
Neoplasms
Lymphocytes
Tumor-Infiltrating Lymphocytes
Neoplasm Staging
Gene Expression Profiling
Immunotherapy
Genes
Monocytes
Immunity
Biomarkers
Immunohistochemistry
Macrophages

Keywords

  • Antitumor immunity
  • Microenvironment
  • Neuroendocrine
  • SCLC
  • TIL

ASJC Scopus subject areas

  • Oncology
  • Pulmonary and Respiratory Medicine

Cite this

Immune Cell Infiltration May Be a Key Determinant of Long-Term Survival in Small Cell Lung Cancer. / Muppa, Prasuna; Parrilha Terra, Simone Barreto Siqueira; Sharma, Anurag; Mansfield, Aaron; Aubry, Marie Christine; Bhinge, Kaustubh; Asiedu, Michael K.; De Andrade, Mariza; Janaki, Nafiseh; Murphy, Stephen J.; Nasir, Aqsa; Van Keulen, Virginia; Vasmatzis, George; Wigle, Dennis A; Yang, Ping; Yi, Eunhee S.; Peikert, Tobias D; Kosari, Farhad.

In: Journal of Thoracic Oncology, Vol. 14, No. 7, 01.07.2019, p. 1286-1295.

Research output: Contribution to journalArticle

Muppa, P, Parrilha Terra, SBS, Sharma, A, Mansfield, A, Aubry, MC, Bhinge, K, Asiedu, MK, De Andrade, M, Janaki, N, Murphy, SJ, Nasir, A, Van Keulen, V, Vasmatzis, G, Wigle, DA, Yang, P, Yi, ES, Peikert, TD & Kosari, F 2019, 'Immune Cell Infiltration May Be a Key Determinant of Long-Term Survival in Small Cell Lung Cancer', Journal of Thoracic Oncology, vol. 14, no. 7, pp. 1286-1295. https://doi.org/10.1016/j.jtho.2019.03.028
Muppa, Prasuna ; Parrilha Terra, Simone Barreto Siqueira ; Sharma, Anurag ; Mansfield, Aaron ; Aubry, Marie Christine ; Bhinge, Kaustubh ; Asiedu, Michael K. ; De Andrade, Mariza ; Janaki, Nafiseh ; Murphy, Stephen J. ; Nasir, Aqsa ; Van Keulen, Virginia ; Vasmatzis, George ; Wigle, Dennis A ; Yang, Ping ; Yi, Eunhee S. ; Peikert, Tobias D ; Kosari, Farhad. / Immune Cell Infiltration May Be a Key Determinant of Long-Term Survival in Small Cell Lung Cancer. In: Journal of Thoracic Oncology. 2019 ; Vol. 14, No. 7. pp. 1286-1295.
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abstract = "Introduction: Although most patients with SCLC die within a few months of diagnosis, a subgroup of patients survive for many years. Factors determining long-term survivorship remain largely unknown. We present the first comprehensive comparative genomic and tumor microenvironment analyses of SCLC between patients with long-term survivorship and patients with the expected survivorship. Methods: We compared surgically resected tumors of 23 long-term SCLC survivors (survival >4 years) and 18 SCLC survivors with the expected survival time (survival ≤2 years). There were no significant differences in clinical variables, including TNM staging and curative- versus non–curative-intent surgery between the groups. Gene expression profiling was performed by using microarrays, and tumor microenvironment analyses were performed by immunohistochemistry of prominent immune-related markers. Results: Immune-related genes and pathways represented the majority of the differentially overexpressed genes in long-term survivorship compared with in expected survivorship. The differences in the immunological tumor microenvironment were confirmed by quantitative immunostaining. Increased numbers of tumor-infiltrating and associated lymphocytes were present throughout tumors of long-term survivors of SCLC. Several differentiating patterns of enhanced antitumor immunity were identified. Although some areas of the tumors of long-term survivors of SCLC also harbored higher numbers of suppressive immune cells (monocytes, regulatory lymphocytes, and macrophages), the ratios of these suppressive cells to CD3-positive lymphocytes were generally lower in the tumors of long-term survivors of SCLC, indicating a less tumor-suppressive microenvironment. Conclusions: Our data demonstrate that long-term survivorship of patients with SCLC is strongly influenced by the presence of the immune cells in the tumor microenvironment. Characterization of the antitumor immune responses may identify opportunities for individualized immunotherapies for SCLC.",
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T1 - Immune Cell Infiltration May Be a Key Determinant of Long-Term Survival in Small Cell Lung Cancer

AU - Muppa, Prasuna

AU - Parrilha Terra, Simone Barreto Siqueira

AU - Sharma, Anurag

AU - Mansfield, Aaron

AU - Aubry, Marie Christine

AU - Bhinge, Kaustubh

AU - Asiedu, Michael K.

AU - De Andrade, Mariza

AU - Janaki, Nafiseh

AU - Murphy, Stephen J.

AU - Nasir, Aqsa

AU - Van Keulen, Virginia

AU - Vasmatzis, George

AU - Wigle, Dennis A

AU - Yang, Ping

AU - Yi, Eunhee S.

AU - Peikert, Tobias D

AU - Kosari, Farhad

PY - 2019/7/1

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N2 - Introduction: Although most patients with SCLC die within a few months of diagnosis, a subgroup of patients survive for many years. Factors determining long-term survivorship remain largely unknown. We present the first comprehensive comparative genomic and tumor microenvironment analyses of SCLC between patients with long-term survivorship and patients with the expected survivorship. Methods: We compared surgically resected tumors of 23 long-term SCLC survivors (survival >4 years) and 18 SCLC survivors with the expected survival time (survival ≤2 years). There were no significant differences in clinical variables, including TNM staging and curative- versus non–curative-intent surgery between the groups. Gene expression profiling was performed by using microarrays, and tumor microenvironment analyses were performed by immunohistochemistry of prominent immune-related markers. Results: Immune-related genes and pathways represented the majority of the differentially overexpressed genes in long-term survivorship compared with in expected survivorship. The differences in the immunological tumor microenvironment were confirmed by quantitative immunostaining. Increased numbers of tumor-infiltrating and associated lymphocytes were present throughout tumors of long-term survivors of SCLC. Several differentiating patterns of enhanced antitumor immunity were identified. Although some areas of the tumors of long-term survivors of SCLC also harbored higher numbers of suppressive immune cells (monocytes, regulatory lymphocytes, and macrophages), the ratios of these suppressive cells to CD3-positive lymphocytes were generally lower in the tumors of long-term survivors of SCLC, indicating a less tumor-suppressive microenvironment. Conclusions: Our data demonstrate that long-term survivorship of patients with SCLC is strongly influenced by the presence of the immune cells in the tumor microenvironment. Characterization of the antitumor immune responses may identify opportunities for individualized immunotherapies for SCLC.

AB - Introduction: Although most patients with SCLC die within a few months of diagnosis, a subgroup of patients survive for many years. Factors determining long-term survivorship remain largely unknown. We present the first comprehensive comparative genomic and tumor microenvironment analyses of SCLC between patients with long-term survivorship and patients with the expected survivorship. Methods: We compared surgically resected tumors of 23 long-term SCLC survivors (survival >4 years) and 18 SCLC survivors with the expected survival time (survival ≤2 years). There were no significant differences in clinical variables, including TNM staging and curative- versus non–curative-intent surgery between the groups. Gene expression profiling was performed by using microarrays, and tumor microenvironment analyses were performed by immunohistochemistry of prominent immune-related markers. Results: Immune-related genes and pathways represented the majority of the differentially overexpressed genes in long-term survivorship compared with in expected survivorship. The differences in the immunological tumor microenvironment were confirmed by quantitative immunostaining. Increased numbers of tumor-infiltrating and associated lymphocytes were present throughout tumors of long-term survivors of SCLC. Several differentiating patterns of enhanced antitumor immunity were identified. Although some areas of the tumors of long-term survivors of SCLC also harbored higher numbers of suppressive immune cells (monocytes, regulatory lymphocytes, and macrophages), the ratios of these suppressive cells to CD3-positive lymphocytes were generally lower in the tumors of long-term survivors of SCLC, indicating a less tumor-suppressive microenvironment. Conclusions: Our data demonstrate that long-term survivorship of patients with SCLC is strongly influenced by the presence of the immune cells in the tumor microenvironment. Characterization of the antitumor immune responses may identify opportunities for individualized immunotherapies for SCLC.

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